The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
Liver PPARα is crucial for whole-body fatty acid homeostasis and is protective against NAFLD
Open accessAbstract
Objective: Peroxisome proliferator-activated receptor α (PPARα) is a nuclear receptor expressed in tissues with high oxidative activity that plays a central role in metabolism. In this work, we investigated the effect of hepatocyte PPARα on non-alcoholic fatty liver disease (NAFLD). Design: We constructed a novel hepatocyte-specific PPARα knockout ( Pparα hep−/− ) mouse model. Using this novel model, we performed transcriptomic analysis following fenofibrate treatment. Next, we investigated which physiological challenges impact on PPARα. Moreover, we measured the contribution of hepatocytic PPARα activity to whole-body metabolism and fibroblast growth factor 21 production during fasting. Finally, we determined the influence of hepatocyte-specific PPARα deficiency in different models of steatosis and during ageing. Results: Hepatocyte PPARα deletion impaired fatty acid catabolism, resulting in hepatic lipid accumulation during fasting and in two preclinical models of steatosis. Fasting mice showed acute PPARα-dependent hepatocyte activity during early night, with correspondingly increased circulating free fatty acids, which could be further stimulated by adipocyte lipolysis. Fasting led to mild hypoglycaemia and hypothermia in Pparα hep−/− mice when compared with Ppar α −/− mice implying a role of PPARα activity in non-hepatic tissues. In agreement with this observation, Pparα −/− mice became overweight during ageing while Ppar α hep−/− remained lean. However, like Ppar α −/− mice, Ppar α hep−/− fed a standard diet developed hepatic steatosis in ageing. Conclusions: Altogether, these findings underscore the potential of hepatocyte PPARα as a drug target for NAFLD.
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Self-citationMolecular mediators of hepatic steatosis and liver injury
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Circulating FGF21 Is Liver Derived and Enhances Glucose Uptake During Refeeding and Overfeeding
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Activating transcription factor 4-dependent induction of FGF21 during amino acid deprivation
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Glucose induces FGF21 mRNA expression through ChREBP activation in rat hepatocytes
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Molecular Actions of PPARα in Lipid Metabolism and Inflammation
Bougarne, N., Weyers, B., Desmet, S. J., Deckers, J., Ray, D. W., Staels, B., & De Bosscher, K. (2018) · Endocrine Reviews · doi:10.1210/er.2018-00064 · Cited by 898
PPARs in Obesity-Induced T2DM, Dyslipidaemia and NAFLD
Gross, B., Pawlak, M., Lefebvre, P., & Staels, B. (2017) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2016.135 · Cited by 778
Li, G., Xie, C., Lu, S., Nichols, R. G., Tian, Y., Li, L., Patel, D., Ma, Y., Brocker, C. N., Yan, T., et al. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.08.019 · Cited by 667
The endocrine function of adipose tissues in health and cardiometabolic disease
Scheja, L., & Heeren, J. (2019) · Nature Reviews Endocrinology · doi:10.1038/s41574-019-0230-6 · Cited by 663
Targeting fibrosis: mechanisms and clinical trials
Zhao, M., Wang, L., Wang, M., Zhou, S., Lu, Y., Cui, H., Racanelli, A. C., Zhang, L., Ye, T., Ding, B., et al. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01070-3 · Cited by 547
Metadata
- Authors
- Montagner, A., Polizzi, A., Fouché, E., Ducheix, S., Lippi, Y., Lasserre, F., Barquissau, V., Régnier, M., Lukowicz, C., Benhamed, F., Iroz, A., Bertrand-Michel, J., Al Saati, T., Cano, P., Mselli-Lakhal, L., Mithieux, G., Rajas, F., Lagarrigue, S., Pineau, T., Loiseau, N., Postic, C., Langin, D., Wahli, W., & Guillou, H.
- Venue
- Gut
- Publisher
- BMJ
- Published
- 2016-02-01
- Volume
- 65
- Issue
- 7
- Pages
- 1202-1214
- ISSN
- 0017-5749 (ISSN-L)
- 1468-3288
- OpenAlex
- W2257770802
- Cited by
- 736
- References
- 9
- FWCI
- 22.87
- Type
- journal article
- Language
- en
- Open access
- hybrid
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