Prolonged sleep restriction induces changes in pathways involved in cholesterol metabolism and inflammatory responses

May combine two claims.

In the SR study, the number of small, medium, and large LDL particles (P after correction <0.01) as well as small VLDL particles (P < 0.05) was decreased after SR compared to BL.

“In the SR study (N = 14 cases, 6 controls), the number of small, medium, and large LDL particles (P after correction <0.01) as well as small VLDL particles (P < 0.05) was decreased after SR compared to BL”

May combine two claims.

There was no significant difference in the levels of any of the LDL or VLDL subclasses in DILGOM, although there was a consistent trend for increase in both LDL and VLDL particles of all sizes.

“There was no significant difference in the levels of any of the LDL or VLDL subclasses, although there was a consistent trend for increase in both LDL and VLDL particles of all sizes”

May combine two claims.

In SR we measured, using the NMR metabolomics, decreased levels of LDL while we found no significant changes in HDL levels.

“In SR we measured, using the NMR metabolomics, decreased levels of LDL while we found no significant changes in HDL levels.”

May combine two claims.

LXRA associated positively with B cells and TLR8, and negatively with ABCA1, NRIP1 and LXRB.

“LXRA associated positively with B cells and TLR8, and negatively with ABCA1, NRIP1 and LXRB.”

May combine two claims.

The genes contributing to these GO pathways in the DILGOM sample were ABCG1, CAV1, NPC1, and NPC1L1, while in the experimental SR study they were ABCA1 and NPC1.

“The genes contributing to these GO pathways in the DILGOM sample were ATP-binding cassette, sub-family G, member 1 (ABCG1), caveolin 1 (CAV1), Niemann-Pick disease, type C1 (NPC1), and Niemann-Pick disease, type C1, gene-like 1 (NPC1L1), while in the experimental SR study they were ABCA1 and NPC1.”

May combine two claims.

ApoB-100 levels decreased (P < 0.005) whereas apoA-I levels did not change in the SR study.

“ApoB-100 levels decreased (P < 0.005) whereas apoA-I (major structural protein in HDL) levels did not change.”

May combine two claims.

In the SSI subjects we found decreased HDL levels but not significant differences in LDL levels.

“In the SSI subjects we found decreased HDL levels but not significant differences in LDL levels.”

May combine two claims.

The common pathways in the experimental SR study and the DILGOM sample were Cholesterol transport, Sterol transport (both P = 0.048), Cholesterol homeostasis and Sterol homeostasis (both with a borderline significance of P = 0.052).

“The common pathways in the experimental SR study and the DILGOM sample were: Cholesterol transport, Sterol transport (both P = 0.048), Cholesterol homeostasis and Sterol homeostasis (both with a borderline significance of P = 0.052) (Table 1).”

May combine two claims.

PE(38:3) was further negatively correlated with TNF-a, which was positively correlated with interleukins 18 and 1 and interferon-γ (IFNG).

“PE(38:3) was further negatively correlated with TNF-a, which was positively correlated with interleukins 18 and 1 and interferon-γ (IFNG).”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The overall prevalence of SSI (mSSI or hSSI) in the YFS sample was 16.2%, quite similar to the 18.2% found in DILGOM.

“Despite the differences in the questions and age groups, the overall prevalence of SSI (mSSI or hSSI), 16.2%, in the YFS sample was quite similar to the 18.2% found in the DILGOM.”

The quote only partly states this claim.

Particularly, scarce associations between the lipids and the immunological variables were observed in control subjects.

“Particularly, scarce associations between the lipids and the immunological variables were observed.”

May combine two claims.

In the present study, the correlation of short sleep duration and subjective sleep insufficiency was P = 2.5E-10 and β = −0.5 h in DILGOM, and P = 4.9E-93 and β = −0.5 h in YFS.

“in the present study, P = 2.5E-10 and β = −0.5 h in DILGOM, and P = 4.9E-93 and β = −0.5 h in YFS”

May combine two claims.

Although the subjects reporting symptoms of OSA reported also more sleep insufficiency, OSA did not explain the difference in HDL, as SSI was independently associated to lower level of large HDL.

“The evaluation of the potential effects of OSA on our results revealed that although the subjects reporting symptoms of OSA reported also more sleep insufficiency, OSA did not explain the difference in HDL, as SSI was independently associated to lower level of large HDL.”

May combine two claims.

In the present SR study, all significant changes from BL to SR, measured using the mass spectrometry technique, were increases, mainly in phosphatidyl ethanolamides, phophatidyl cholines, triglycerides and cholesterol esters.

“In the present SR study, all significant changes from BL to SR, measured using the mass spectrometry technique, were increases, mainly in phosphatidyl ethanolamides, phophatidyl cholines, triglycerides and cholesterol esters.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

A total of 530 lipids were detected and 330 identified.

“A total of 530 lipids were detected and 330 identified.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Hierarchical clustering analysis using principal components revealed that the 135 metabolites cluster into 21 clusters that explain 95% of the variance.

“Hierarchical clustering analysis using principal components revealed that the 135 metabolites cluster into 21 clusters that explain 95% of the variance.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Saliva cortisol was assessed 10 times per day during the experiment, and only a modest, 16 min on average, delay in the circadian phase measured by the morning peak of cortisol was observed in the sleep-deprived cases.

“Saliva cortisol was assessed 10 times per day during the experiment, and only a modest, 16 min on average, delay in the circadian phase measured by the morning peak of cortisol (from mean ± s.d. 07:39 ± 0:14 in BL to 07:55 ± 0:11 in SR) was observed in the sleep-deprived cases75.”

• cites [75] van Leeuwen, W. M. et al. Prolonged sleep restriction affects glucose metabolism in healthy young men. Int. J. Endocrinol. 2010, 108641 (2010). sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Total sleep duration in the cases (N = 14) decreased from 7 h 22 min ± 20 min in BL to 3 h 54 min ± 5 min in SR, while it remained relatively constant, 7 h 19 min ± 16 min to 7 h 26 min ± 17 min at the same timepoints, in the controls (N = 7).

“Total sleep duration in the cases (N = 14) decreased from 7 h 22 min ± 20 min in BL to 3 h 54 min ± 5 min in SR, while it remained relatively constant, 7 h 19 min ± 16 min to 7 h 26 min ± 17 min at the same timepoints, in the controls (N = 7).”

Probably not a substantial claim: may not pass S3 (load-bearing).

The prevalence of probable self-reported OSA in the YFS sample using the described criteria was 5%.

“The prevalence of probable self-reported OSA in the YFS sample using these criteria was 5%.”

Classified as probably not a substantial claim.

Assessment of circulating lipid profiles using NMR spectroscopy allows detailed characterization of many lipoprotein features at the subclass level, including particle size.

“The assessment of circulating lipid profiles using nuclear magnetic resonance (NMR) spectroscopy goes beyond the typically measured total lipids, like total cholesterol and triglycerides, and allows detailed characterization of many lipoprotein features at the subclass level, including the size of the particles”

• cites [1617]Not checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

Decrease in HDL has been regarded as one important risk factor for cardiovascular diseases.

“Decrease in HDL has been regarded as one important risk factor for cardiovascular diseases40.”

• cites [40] Rosenson, R. S. et al. Dysfunctional HDL and atherosclerotic cardiovascular disease. Nat. Rev. Cardiol. 13, 48–60 (2016). sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

The prevalence of 'sleep debt' using closely similar criterion as used in the YFS sample has been earlier found to be 20% in 1004 French young adults.

“In accordance with these results, the prevalence of “sleep debt”, using closely similar criterion as used in the YFS sample, has been earlier found to be 20% in 1004 French young adults27.”

• cites [27] Leger, D. et al. Short sleep in young adults: Insomnia or sleep debt? Prevalence and clinical description of short sleep in a representative sample of 1004 young adults from France. Sleep Med. 12, 454–462 (2011). sourceNot checked yet

  Not checked in the free run.

Classified as probably not a substantial claim.

In a cross-sectional study we cannot provide direct evidence on the duration of SSI for those who reported it.

“However, in a cross-sectional study we cannot provide direct evidence on the duration of SSI for those who reported it.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

HDL can protect against atherosclerosis by multiple mechanisms, including the ability to efflux cholesterol from endothelial macrophages (macrophage reverse cholesterol transport), or through anti-inflammatory, antioxidative and antiapoptotic pathways.

“HDL can protect against atherosclerosis by multiple mechanisms, including the ability to efflux cholesterol from endothelial macrophages (macrophage reverse cholesterol transport)43, or through anti-inflammatory44, antioxidative45 and antiapoptotic46 pathways.”

• cites [43] Rosenson, R. S. et al. Cholesterol efflux and atheroprotection: advancing the concept of reverse cholesterol transport. Circulation 125, 1905–1919 (2012). sourceNot checked yet

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• cites [44] Haas, M. J. & Mooradian, A. D. Inflammation, high-density lipoprotein and cardiovascular dysfunction. Curr. Opin. Infect. Dis. 24, 265–272 (2011). sourceNot checked yet

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• cites [45] Karlsson, H., Kontush, A. & James, R. W. Functionality of HDL: antioxidation and detoxifying effects. Handb. Exp. Pharmacol. 224, 207–228 (2015). sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

It has been shown that serum triglyceride levels decreased following restriction of sleep to 4 hours on 5 consecutive nights.

“It has been shown that serum triglyceride levels decreased following restriction of sleep to 4 hours on 5 consecutive nights12”

• cites [12] Reynolds, A. C. et al. Impact of five nights of sleep restriction on glucose metabolism, leptin and testosterone in young adult men. Plos One 7, e41218 (2012). sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

One study used NMR to assess urine metabolites in short-term sleep deprivation.

“while one study used NMR to assess urine metabolites in short-term sleep deprivation24”

• cites [24] Giskeødegård, G. F., Davies, S. K., Revell, V. L., Keun, H. & Skene, D. J. Diurnal rhythms in the human urine metabolome during sleep and total sleep deprivation. Sci. Rep. 5, 14843 (2015). sourceNot checked yet

  Not checked in the free run.

May combine two claims.

The lipoprotein profile showed decreased LDL in experimental SR, resembling LDL changes in acute-phase response, but in epidemiological SSI large HDL was decreased.

“Interestingly, the lipoprotein profile showed decreased LDL in experimental SR, resembling LDL changes in acute-phase response39, but in epidemiological SSI large HDL was decreased.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Pharmacological increase of serum HDL levels has not affected the risk of cardiovascular diseases.

“Particularly the latter approach has been a disappointment: pharmacological increase of serum HDL levels has not affected the risk of cardiovascular diseases42”

• cites [42] Tariq, S. M., Sidhu, M. S., Toth, P. P. & Boden, W. E. HDL hypothesis: where do we stand now? Curr. Atheroscler. Rep. 16, 398 (2014). sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

In a recent study, no changes in blood total cholesterol, LDL, HDL, or triglycerides were found after sleep restriction to 4 hours on 5 nights.

“In a recent study, no changes in blood total cholesterol, LDL, HDL, or triglycerides were found after sleep restriction to 4 hours on 5 nights14.”

• cites [14] O’Keeffe, M., Roberts, A. L., Kelleman, M., Roychoudhury, A. & St-Onge, M. P. No effects of short-term sleep restriction, in a controlled feeding setting, on lipid profiles in normal-weight adults. J. Sleep Res. 22, 717–720 (2013). sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

Myeloperoxidase-modified LDL particles increased under similar conditions.

“and also that myeloperoxidase-modified LDL particles increased under similar conditions13.”

• cites [13] Boudjeltia, K. Z. et al. Temporal dissociation between myeloperoxidase (MPO)-modified LDL and MPO elevations during chronic sleep restriction and recovery in healthy young men. Plos One 6, e28230 (2011). sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

The classical view on the relationship between serum lipid levels and risk for cardiovascular events states that serum high LDL and low HDL cholesterol level is a risk combination for cardiovascular events.

“The classical view on the relationship between serum lipid levels and risk for cardiovascular events, formulated based on the findings of the Framingham study41 and since confirmed by many epidemiological studies, states that serum high LDL and low HDL cholesterol level is a risk combination for cardiovascular events42.”

• cites [41] Gordon, T., Castelli, W. P., Hjortland, M. C., Kannel, W. B. & Dawber, T. R. High density lipoprotein as a protective factor against coronary heart disease. The Framingham Study. Am. J. Med. 62, 707–714 (1977). sourceNot checked yet

  Not checked in the free run.

• cites [42] Tariq, S. M., Sidhu, M. S., Toth, P. P. & Boden, W. E. HDL hypothesis: where do we stand now? Curr. Atheroscler. Rep. 16, 398 (2014). sourceNot checked yet

  Not checked in the free run.

Classified as probably not a substantial claim. May combine two claims.

An important transcriptional regulator of the RCT is the nuclear liver X receptor (LXR) signalling, which promotes RCT and decreases inflammation.

“An important transcriptional regulator of the RCT is the nuclear liver X receptor (LXR) signalling, which promotes RCT and decreases inflammation303132.”

• cites 303132Not checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

For the epidemiological samples, age and gender were adjusted for in the linear regression model.

“For the epidemiological samples, age and gender were adjusted for in the linear regression model.”

May combine two claims.

The one week experimental SR may have been too short to affect the number of HDL particles, while in the epidemiological samples, the number of large HDL particles was lower among those who reported insufficient sleep.

“The one week experimental SR may have been too short to affect the number of HDL particles, while in the epidemiological samples, the number of large HDL particles was lower among those who reported insufficient sleep.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Modulations in HDL particle composition can transform it to dysfunctional and, through this modulation, increase the risk of CVD.

“Moreover, modulations in HDL particle composition can transform it to dysfunctional and, through this modulation, increase the risk of CVD40.”

• cites [40] Rosenson, R. S. et al. Dysfunctional HDL and atherosclerotic cardiovascular disease. Nat. Rev. Cardiol. 13, 48–60 (2016). sourceNot checked yet

  Not checked in the free run.

May combine two claims.

The changes were detected at the level of transcriptome as well as in the circulating lipid profile.

“The changes were detected at the level of transcriptome as well as in the circulating lipid profile.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The negative association between TLR4 and NPC1/ABCA1 is expected if LXR activity was decreased.

“as would be expected if LXR activity was decreased.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Analysis of circulating lipid molecules based on mass spectrometry has previously been applied in circadian research.

“Analysis of circulating lipid molecules based on mass spectrometry (MS), which gives an extensive profile of individual lipid molecules but does not quantify lipoprotein-related measures, has previously been applied in circadian research18192021.”

• cites 18192021Not checked yet

  Not checked in the free run.

May combine two claims.

At gene expression level, the activation included increases in expression of toll-like receptors, NF-kB signalling pathway and interleukin-8 production pathways.

“At gene expression level, the activation included increases in expression of toll-like receptors, NF-kB signalling pathway and interleukin-8 production pathways5.”

• cites [5] Aho, V. et al. Partial sleep restriction activates immune response-related gene expression pathways: experimental and epidemiological studies in humans. Plos One 8, e77184 (2013). sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

This route of removal of cholesterol (macrophage RCT) has been regarded as an important (but not only) component in retaining cholesterol balance in arterial endothelium.

“However, this route of removal of cholesterol (macrophage RCT) has been regarded as an important (but not only) component in retaining cholesterol balance in arterial endothelium43.”

• cites [43] Rosenson, R. S. et al. Cholesterol efflux and atheroprotection: advancing the concept of reverse cholesterol transport. Circulation 125, 1905–1919 (2012). sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing).

Since the relationship between cholesterol transporter expression in white blood cells and serum HDL concentration is far from simple, it is difficult to evaluate how the observed expression changes were reflected to the flow of cholesterol from macrophages to liver and finally feces (RCT).

“Since the relationship between cholesterol transporter expression in white blood cells and serum HDL concentration is far from simple, it is difficult to evaluate how the observed expression changes were reflected to the flow of cholesterol from macrophages to liver and finally feces (RCT)”

Probably not a substantial claim: may not pass S3 (load-bearing).

The modifications differ according to the nature of the event that aroused the reaction, e.g. surgical trauma and infection.

“Moreover, the modifications differ according to the nature of the event that aroused the reaction, e.g. surgical trauma and infection6668.”

• cites [66] Carpentier, Y. A. & Scruel, O. Changes in the concentration and composition of plasma lipoproteins during the acute phase response. Curr. Opin. Clin. Nutr. Metab. Care 5, 153–158 (2002). sourceNot checked yet

  Not checked in the free run.

• cites [68] Hotamisligil, G. S. Inflammation and metabolic disorders. Nature 444, 860–867 (2006). sourceNot checked yet

  Not checked in the free run.

Classified as probably not a substantial claim. May combine two claims.

Caveolin-1 (CAV1) is found in caveolae, cholesterol-rich membrane lipid formations that are involved in cholesterol traffic and homeostasis and regulation of inflammation.

“Caveolin-1 (CAV1) is found in caveolae, cholesterol-rich membrane lipid formations that are involved in cholesterol traffic and homeostasis58 and regulation of inflammation59 among other functions.”

• cites [58] Fielding, C. J. & Fielding, P. E. Caveolae and intracellular trafficking of cholesterol. Adv. Drug Deliv. Rev. 49, 251–264 (2001). sourceNot checked yet

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• cites [59] Chidlow, J. H., Jr & Sessa, W. C. Caveolae, caveolins, and cavins: complex control of cellular signalling and inflammation. Cardiovasc. Res. 86, 219–225 (2010). sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

ABCA1 deficiency in Tangier disease leads to very low or absent HDL levels and larger VLDL particles.

“ABCA1 deficiency in Tangier disease leads to very low or absent HDL levels and larger VLDL particles56.”

• cites [56] Liu, M., Chung, S., Shelness, G. S. & Parks, J. S. Hepatic ABCA1 and VLDL triglyceride production. Biochim. Biophys. Acta 1821, 770–777 (2012). sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Sleep loss is often accompanied with circadian misalignment, also known to cause changes in the regulation of the immune system and metabolism and associate to cardiovascular diseases.

“Sleep loss is often accompanied with circadian misalignment, also known to cause changes in the regulation of the immune system and metabolism and associate to cardiovascular diseases7273.”

• cites [72] Bass, J. & Takahashi, J. S. Circadian integration of metabolism and energetics. Science 330, 1349–1354 (2010). sourceNot checked yet

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• cites [73] Machado, R. M. & Koike, M. K. Circadian rhythm, sleep pattern, and metabolic consequences: an overview on cardiovascular risk factors. Horm. Mol. Biol. Clin. Investig. 18, 47–52 (2014). sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

The participants of the experimental study were carefully screened not to have any (sleep) disorders.

“While the participants of the experimental study were carefully screened not to have any (sleep) disorders”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Previous studies indicate that the immune system is activated during experimental sleep restriction, and in persons who in epidemiological studies report short sleep duration.

“Previous studies indicate that the immune system is activated during experimental sleep restriction, and in persons who in epidemiological studies report short sleep duration (reviewed in6465).”

• cites [64] Faraut, B., Boudjeltia, K. Z., Vanhamme, L. & Kerkhofs, M. Immune, inflammatory and cardiovascular consequences of sleep restriction and recovery. Sleep Med. Rev. 16, 137–149 (2012). sourceNot checked yet

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• cites [65] Mullington, J. M., Simpson, N. S., Meier-Ewert, H. K. & Haack, M. Sleep loss and inflammation. Best Pract. Res. Clin. Endocrinol. Metab. 24, 775–784 (2010). sourceNot checked yet

  Not checked in the free run.

May combine two claims.

In the acute SR study, only increases in lipid levels were observed after the deprivation period, while in the partial SR study also declines were recorded.

“In the acute SR study22, only increases in lipid levels were observed after the deprivation period, while in the partial SR study23 also declines were recorded.”

• cites [22] Davies, S. K. et al. Effect of sleep deprivation on the human metabolome. Proc. Natl. Acad. Sci. USA 111, 10761–6 (2014). sourceNot checked yet

  Not checked in the free run.

• cites [23] Weljie, A. M. et al. Oxalic acid and diacylglycerol 36:3 are cross-species markers of sleep debt. Proc. Natl. Acad. Sci. USA 112, 2569–2574 (2015). sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

It is unclear to which extent the results reflect changes in the actual metabolic processes.

“Thus it is unclear to which extent the results reflect changes in the actual metabolic processes.”

• AssumptionRests on an assumption: The main regulation of metabolism takes place in other tissues (e.g. liver, pancreas) than blood cells, which were used in the gene expression analyses.

May combine two claims.

In epidemiological studies sleep duration and self-reported sleep insufficiency have shown independent effects on cardiovascular outcomes (including hypertension, cholesterol level and cardiac events) and performance.

“In epidemiological studies sleep duration and self-reported sleep insufficiency have shown independent effects on cardiovascular outcomes (including hypertension, cholesterol level and cardiac events)70 and performance71.”

• cites [70] Altman, N. G. et al. Sleep duration versus sleep insufficiency as predictors of cardiometabolic health outcomes. Sleep Med. 13, 1261–1270 (2012). sourceNot checked yet

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• cites [71] Abe, T., Komada, Y. & Inoue, Y. Short sleep duration, snoring and subjective sleep insufficiency are independent factors associated with both falling asleep and feeling sleepiness while driving. Intern. Med. 51, 3253–3260 (2012). sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Both the down-regulation of RCT pathway and up-regulation of the inflammatory pathways could result from a decrease of LXR activity.

“Thus both the down-regulation of RCT pathway and up-regulation of the inflammatory pathways could result from a decrease of LXR activity (Fig. 3).”

• cites [39] Venteclef, N., Jakobsson, T., Steffensen, K. R. & Treuter, E. Metabolic nuclear receptor signaling and the inflammatory acute phase response. Trends Endocrinol. Metab. 22, 333–343 (2011). sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

Many acute conditions, including surgical trauma, myocardial infarction and inflammation, induce the systemic acute phase reaction (APR), with acute phase protein production in the liver as an integral part of the host defence response.

“Many acute conditions, including surgical trauma, myocardial infarction and inflammation, induce the systemic acute phase reaction (APR), with acute phase protein production in the liver as an integral part of the host defence response.”

• cites [66] Carpentier, Y. A. & Scruel, O. Changes in the concentration and composition of plasma lipoproteins during the acute phase response. Curr. Opin. Clin. Nutr. Metab. Care 5, 153–158 (2002). sourceNot checked yet

  Not checked in the free run.

• cites [67] Khovidhunkit, W. et al. Effects of infection and inflammation on lipid and lipoprotein metabolism: mechanisms and consequences to the host. J. Lipid Res. 45, 1169–1196 (2004). sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Some other studies have not found an effect of CAV1 on cholesterol efflux, and the overall effect of CAV1 on cholesterol efflux is complex.

“Some other studies have not found an effect6263, and the overall effect of CAV1 on cholesterol efflux is complex61.”

• cites [61] Gu, H. M., Wang, F. Q. & Zhang, D. W. Caveolin-1 interacts with ATP binding cassette transporter G1 (ABCG1) and regulates ABCG1-mediated cholesterol efflux. Biochim. Biophys. Acta 1841, 847–858 (2014). sourceNot checked yet

  Not checked in the free run.

• cites [62] Wang, L. et al. Caveolin-1 does not affect SR-BI-mediated cholesterol efflux or selective uptake of cholesteryl ester in two cell lines. J. Lipid Res. 44, 807–815 (2003). sourceNot checked yet

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• cites [63] Terasaka, N. et al. ATP-binding cassette transporter G1 and high-density lipoprotein promote endothelial NO synthesis through a decrease in the interaction of caveolin-1 and endothelial NO synthase. Arterioscler. Thromb. Vasc. Biol. 30, 2219–2225 (2010). sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

If the inflammation-sustaining condition continues, as presumably in the epidemiological SSI groups of the present study, the metabolic modifications may develop further and become chronic.

“However, if the inflammation-sustaining condition continues, as presumably in the epidemiological SSI groups of the present study, the metabolic modifications may develop further and become chronic3968.”

• cites [39] Venteclef, N., Jakobsson, T., Steffensen, K. R. & Treuter, E. Metabolic nuclear receptor signaling and the inflammatory acute phase response. Trends Endocrinol. Metab. 22, 333–343 (2011). sourceNot checked yet

  Not checked in the free run.

• cites [68] Hotamisligil, G. S. Inflammation and metabolic disorders. Nature 444, 860–867 (2006). sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

The effects of age and gender have been addressed by including them in the linear models used for statistical analyses.

“The effects of these factors have been addressed by including them in the linear models used for statistical analyses.”

Classified as probably not a substantial claim.

CAV1 has been proposed to participate in the regulation of cholesterol efflux to HDL, possibly in interaction with ABCG1.

“CAV1 has been proposed to participate in the regulation of cholesterol efflux to HDL6061, possibly in interaction with ABCG161.”

• cites [60] Mukhamedova, N. et al. Enhancing apolipoprotein A-I-dependent cholesterol efflux elevates cholesterol export from macrophages in vivo . J. Lipid Res. 49, 2312–2322 (2008). sourceNot checked yet

  Not checked in the free run.

• cites [61] Gu, H. M., Wang, F. Q. & Zhang, D. W. Caveolin-1 interacts with ATP binding cassette transporter G1 (ABCG1) and regulates ABCG1-mediated cholesterol efflux. Biochim. Biophys. Acta 1841, 847–858 (2014). sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

In addition to changes in protein synthesis, also lipid metabolism undergoes significant modifications in APR.

“In addition to changes in protein synthesis, also lipid metabolism undergoes significant modifications in APR6667.”

• cites [66] Carpentier, Y. A. & Scruel, O. Changes in the concentration and composition of plasma lipoproteins during the acute phase response. Curr. Opin. Clin. Nutr. Metab. Care 5, 153–158 (2002). sourceNot checked yet

  Not checked in the free run.

• cites [67] Khovidhunkit, W. et al. Effects of infection and inflammation on lipid and lipoprotein metabolism: mechanisms and consequences to the host. J. Lipid Res. 45, 1169–1196 (2004). sourceNot checked yet

  Not checked in the free run.

May combine two claims.

In the present study, NMR spectroscopy measurement was able to track changes in lipid profiles under conditions of restricted sleep, further confirming that this condition modifies lipid metabolism.

“In the present study, also NMR spectroscopy measurement was able to track changes in lipid profiles under conditions of restricted sleep, further confirming that this condition modifies lipid metabolism.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Metabolic modifications aim at optimization of the defence, and would return to baseline level after the need for defence has disappeared.

“Metabolic modifications aim at optimization of the defence, and would return to baseline level after the need for defence has disappeared68.”

• cites [68] Hotamisligil, G. S. Inflammation and metabolic disorders. Nature 444, 860–867 (2006). sourceNot checked yet

  Not checked in the free run.

Classified as probably not a substantial claim. May combine two claims.

While cytokines (including IL-1b, IL-6 and TNF-a) are central regulators of the APR, recent research suggests that an important part of the metabolic regulation in APR is channelled via nuclear receptors, including LXR, PPAR and LHR-1.

“While cytokines (including IL-1b, IL-6 and TNF-a) are central regulators of the APR, recent research suggests that an important part of the metabolic regulation in APR is channelled via nuclear receptors, including LXR, PPAR and LHR-139.”

• cites [39] Venteclef, N., Jakobsson, T., Steffensen, K. R. & Treuter, E. Metabolic nuclear receptor signaling and the inflammatory acute phase response. Trends Endocrinol. Metab. 22, 333–343 (2011). sourceNot checked yet

  Not checked in the free run.

May combine two claims.

We have earlier shown that cytokine (interleukins IL-1b, IL-6 and IL-17) release as response to in vitro immunological challenge is increased after sleep restriction, as well as serum acute phase protein CRP.

“We have earlier shown that cytokine (interleukins IL-1b, IL-6 and IL-17) release as response to in vitro immunological challenge is increased after sleep restriction, as well as serum acute phase protein CRP7.”

• cites [7] van Leeuwen, W. M. et al. Sleep restriction increases the risk of developing cardiovascular diseases by augmenting proinflammatory responses through IL-17 and CRP. Plos One 4, e4589 (2009). sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

An additional source of variation lies in the differences in age and gender between the populations studied.

“An additional source of variation lies in the differences in age and gender between the populations studied.”

Classified as probably not a substantial claim.

In the SR experiment, participants were subjected to only one cycle.

“In the SR experiment, participants were subjected to only one cycle.”

Classified as probably not a substantial claim.

In the sleep laboratory, the participants were randomly allocated to the experimental group ('cases'; N = 14) or the control group ('controls', N = 8).

“In the sleep laboratory, the participants were randomly allocated to the experimental group (“cases”; N = 14) or the control group (“controls”, N = 8)”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The Young Finns Study participants were randomly selected in 5 centres in Finland.

“The study participants were randomly selected in 5 centres in Finland.”

Classified as probably not a substantial claim.

NMR-based analyses provide absolute quantification of multiple serum metabolites, including lipoprotein subclass distribution, fatty acids, and various small molecules including amino acids and glycolysis precursors.

“The NMR-based analyses provide absolute quantification of multiple serum metabolites, including lipoprotein subclass distribution, fatty acids, and various small molecules including amino acids and glycolysis precursors (Supplementary Table S3).”

• cites 252986Not checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

LCAT activity was assessed by measuring cholesterol esterification activity using exogenous [3H]cholesterol-labelled HDL proteoliposome discs as the substrate.

“LCAT activity was assessed by measuring cholesterol esterification activity using exogenous [3H]cholesterol-labelled HDL proteoliposome discs as the substrate91.”

• cites [91] Jauhiainen, M. & Dolphin, P. J. Human plasma lecithin-cholesterol acyltransferase. An elucidation of the catalytic mechanism. J. Biol. Chem. 261, 7032–7043 (1986). sourceNot checked yet

  Not checked in the free run.

Classified as probably not a substantial claim. May combine two claims.

Unlike pairwise measures of association such as Pearson correlation coefficient, partial correlation provides a stronger criterion for dependency by adjusting for confounding effects, and thus removing spurious associations to a large extent.

“Unlike the pairwise measures of associations such as Pearson correlation coefficient, partial correlation provides a stronger criterion for dependency by adjusting for confounding effects, and thus removing spurious associations to a large extent.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

NMR-based metabolite profiling has previously been used in various epidemiological and genetic studies, and details of the method have been described.

“The NMR-based metabolite profiling has previously been used in various epidemiological and genetic studies838485 and details of the method have been described252986.”

• cites 838485Not checked yet

  Not checked in the free run.

• cites 252986Not checked yet

  Not checked in the free run.

Classified as probably not a substantial claim.

CETP activity was analysed as the transfer/exchange of radiolabelled [14C]cholesteryl oleate between exogenously added human LDL and HDL2, as described in the cited protocol.

“CETP activity was analysed as the transfer/exchange of radiolabelled [14C]cholesteryl oleate between exogenously added human LDL and HDL2, as described in89.”

• cites [89] Groener, J. E., Pelton, R. W. & Kostner, G. M. Improved estimation of cholesteryl ester transfer/exchange activity in serum or plasma. Clin. Chem. 32, 283–286 (1986). sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

The Cardiovascular Risk in Young Finns Study was approved by the ethics committees of University Hospitals of Turku, Helsinki, Tampere, Kuopio, and Oulu.

“The Cardiovascular Risk in Young Finns Study was approved by the ethics committees of University Hospitals of Turku, Helsinki, Tampere, Kuopio, and Oulu.”

Probably not a substantial claim: may not pass S3 (load-bearing).

One control subject was excluded after the EEG analysis as he had been sleeping less than 6 h/night during the experiment.

“One control subject was excluded after the EEG analysis as he had been sleeping less than 6 h/night during the experiment.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Serum PON1 activity was measured using a spectroscopy method and Paraoxon (diethyl-p-nitrophenyl phosphate; Sigma) as the substrate.

“Serum PON1 activity was measured using spectroscopy method and Paraoxon (diethyl-p-nitrophenyl phosphate; Sigma) as the substrate92.”

• cites [92] Kleemola, P. et al. Dietary determinants of serum paraoxonase activity in healthy humans. Atherosclerosis 160, 425–432 (2002). sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S1 (asserted), S3 (load-bearing), S4 (based).

In the YFS cohort, linear regression was used to correlate RNA expression with SSI, adjusting for age and gender.

“Linear regression was used to correlate RNA expression with SSI, adjusting for age and gender (R version 2.14).”

• AssumptionRests on an assumption: Subjective sleep insufficiency, as assessed by the questionnaire items and the difference between sleep need and sleep duration, is a valid measure of insufficient sleep.

Classified as probably not a substantial claim.

Ultra Performance Liquid Chromatography (UPLC) coupled to electrospray ionization quadrupole time-of-flight mass spectrometry (QTOFMS) was used with the established protocol.

“Ultra Performance Liquid Chromatography (UPLC) coupled to electrospray ionization quadrupole time-of-flight mass spectrometry (QTOFMS) was used with the established protocol87.”

• cites [87] Nygren, H., Seppanen-Laakso, T., Castillo, S., Hyotylainen, T. & Oresic, M. Liquid chromatography-mass spectrometry (LC-MS)-based lipidomics for studies of body fluids and tissues. Methods Mol. Biol. 708, 247–257 (2011). sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

Possible self-reported OSA was estimated using questions addressing the frequency and quality of snoring, as described earlier.

“Possible self-reported OSA was estimated using questions addressing the frequency and quality of snoring, as described earlier81.”

• cites [81] Niiranen, T. J., Kronholm, E., Rissanen, H., Partinen, M. & Jula, A. M. Self-reported obstructive sleep apnea, simple snoring, and various markers of sleep-disordered breathing as predictors of cardiovascular risk. Sleep Breath doi: 10.1007/s11325-015-1253-4 (2015). sourceNot checked yet

  Not checked in the free run.

May combine two claims.

These responses modulate lipid metabolism, possibly through LXRs, and in the long run may contribute to the increased risk of cardiovascular diseases.

“These responses modulate lipid metabolism, possibly through LXRs, and in the long run may contribute to the increased risk of cardiovascular diseases.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

This study was conducted according to the Declaration of Helsinki principles, and written informed consent was obtained from all participants.

“This study was conducted according to the Declaration of Helsinki principles, and written informed consent was obtained from all participants.”

Classified as probably not a substantial claim.

P values from the t tests were corrected with the amount of clusters (N = 21).

“P values from the t tests were corrected with the amount of clusters (N = 21).”

Classified as probably not a substantial claim.

Partial correlation is particularly favourable for integrating multiple layers of information as in this study, because it inherently filters out false positives by discovering only direct interactions with high confidence.

“This is particularly favourable for an integration of multiple layers of information as in our study, because it inherently filters out false positives by discovering only direct interactions with high confidence.”

Probably not a substantial claim: may not pass S3 (load-bearing).

In the YFS cohort, the RNA isolating process was validated by analysing the integrity of RNA with the RNA 6000 Nano Chip Kit (Agilent).

“The RNA isolating process was validated by analysing the integrity of RNA with the RNA 6000 Nano Chip Kit (Agilent).”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

In our experimental SR study, the modest delay (16 min) in circadian rhythm, measured in the morning salivary cortisol peak, is unlikely to significantly modulate the results, but the effect cannot be entirely ruled out.

“In our experimental SR study, the modest delay (16 min) in circadian rhythm, measured in the morning salivary cortisol peak, is unlikely to significantly modulate the results, but the effect cannot be entirely ruled out.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

In the DILGOM cohort, technical replicates were combined via a bead-count weighted average, and replicates with Pearson's correlation coefficient <0.94 or Spearman's rank correlation coefficient <0.60 were removed from further analysis.

“Technical replicates were combined via a bead-count weighted average, and replicates with Pearson’s correlation coefficient <0.94 or Spearman’s rank correlation coefficient <0.60 were removed from further analysis.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Polygraphy was measured continuously and EEG scored according to the Rechtschaffen-Kales manual.

“Polygraphy was measured continuously and EEG scored according to the Rechtschaffen-Kales manual7577.”

• cites [7577]Not checked yet

  Not checked in the free run.

Classified as probably not a substantial claim.

In the DILGOM cohort, linear regression was used to correlate RNA expression with SSI, adjusting for age and gender.

“Linear regression was used to correlate RNA expression with SSI, adjusting for age and gender (R version 2.14).”

• AssumptionRests on an assumption: Subjective sleep insufficiency, as assessed by the questionnaire items and the difference between sleep need and sleep duration, is a valid measure of insufficient sleep.

Classified as probably not a substantial claim.

The lipidomic data was normalised using internal standards representative of each class of lipid present in the samples.

“The data was normalised using internal standards representative of each class of lipid present in the samples.”

Probably not a substantial claim: may not pass S3 (load-bearing).

In the DILGOM and YFS epidemiological samples, linear regression was used to correlate NMR metabolites with SSI, adjusting for age and gender.

“In the epidemiological samples DILGOM and YFS, linear regression was used to correlate NMR metabolites with SSI, adjusting for age and gender (R version 3.0), similarly as was done in the gene expression analysis.”

• AssumptionRests on an assumption: Subjective sleep insufficiency, as assessed by the questionnaire items and the difference between sleep need and sleep duration, is a valid measure of insufficient sleep.

Probably not a substantial claim: may not pass S3 (load-bearing).

PLTP activity was assessed with phosphatidylcholine liposomes following an earlier reported protocol.

“PLTP activity was assessed with phosphatidylcholine liposomes following an earlier reported protocol90.”

• cites [90] Jauhiainen, M. et al. Human plasma phospholipid transfer protein causes high density lipoprotein conversion. J. Biol. Chem. 268, 4032–4036 (1993). sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

In the YFS cohort, the expression analysis was successful for 1650 subjects.

“The expression analysis was successful for 1650 subjects.”

Classified as probably not a substantial claim. May combine two claims.

In these networks, non-missing edges denote non-zero partial correlations (P < 0.05) between pairs of variables and thus imply direct interactions.

“In these networks non-missing edges denote non-zero partial correlations (P < 0.05) between pairs of variables and thus imply direct interactions.”

Probably not a substantial claim: may not pass S3 (load-bearing).

In the YFS sample, the analyses were run also with self-reported probable OSA added in the model.

“In the YFS sample, the analyses were run also with self-reported probable OSA added in the model.”

• AssumptionRests on an assumption: Subjective sleep insufficiency, as assessed by the questionnaire items and the difference between sleep need and sleep duration, is a valid measure of insufficient sleep.

Probably not a substantial claim: may not pass S3 (load-bearing).

The experimental sleep restriction study protocol and the FINRISK 2007 study including the DILGOM subsample were approved by the coordinating ethics committee of the Hospital District of Helsinki.

“The experimental sleep restriction study protocol and the FINRISK 2007 study including the DILGOM subsample were approved by the coordinating ethics committee of the Hospital District of Helsinki.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

In the YFS cohort, blood samples were collected after overnight fasting; 97.4% of subjects reported fasting overnight as requested, 1.3% did not, and no information on fasting was obtained for 1.4%.

“Blood samples were collected after overnight fasting (97.4% of the subjects reported to have fasted overnight before the sample taking as requested and 1.3% not to have, while no information on fasting was obtained for 1.4%).”