CoChat
Sign Up
Cited by 566Adipokines, Inflammation, and Metabolic DiseasesAdipose Tissue and MetabolismDiet, Metabolism, and Disease

The DOI matches its Crossref record; 28 of the 28 references it cites were found in a registry or an index.

Inflammation Is Necessary for Long-Term but Not Short-Term High-Fat Diet–Induced Insulin Resistance

Open access
Lee, Yun Sok, Li, Pingping, Huh, Jin Young, Hwang, In Jae, Lu, Min, Kim, Jong In, Ham, Mira, Talukdar, Saswata, Chen, Ai, Lu, Wendell J., Bandyopadhyay, Guatam K., Schwendener, Reto, Olefsky, Jerrold, Kim, Jae Bum·2011·Diabetes
DOI 10.2337/db11-0194PMC PMC3178297
Open this paper in CoChat — free accountOpen PDF

Abstract

OBJECTIVE: Tissue inflammation is a key factor underlying insulin resistance in established obesity. Several models of immuno-compromised mice are protected from obesity-induced insulin resistance. However, it is unanswered whether inflammation triggers systemic insulin resistance or vice versa in obesity. The purpose of this study was to assess these questions. RESEARCH DESIGN AND METHODS: We fed a high-fat diet (HFD) to wild-type mice and three different immuno-compromised mouse models (lymphocyte-deficient Rag1 knockout, macrophage-depleted, and hematopoietic cell-specific Jun NH2-terminal kinase–deficient mice) and measured the time course of changes in macrophage content, inflammatory markers, and lipid accumulation in adipose tissue, liver, and skeletal muscle along with systemic insulin sensitivity. RESULTS: In wild-type mice, body weight and adipose tissue mass, as well as insulin resistance, were clearly increased by 3 days of HFD. Concurrently, in the short-term HFD period inflammation was selectively elevated in adipose tissue. Interestingly, however, all three immuno-compromised mouse models were not protected from insulin resistance induced by the short-term HFD. On the other hand, lipid content was markedly increased in liver and skeletal muscle at day 3 of HFD. CONCLUSIONS: These data suggest that the initial stage of HFD-induced insulin resistance is independent of inflammation, whereas the more chronic state of insulin resistance in established obesity is largely mediated by macrophage-induced proinflammatory actions. The early-onset insulin resistance during HFD feeding is more likely related to acute tissue lipid overload.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.2337/db11-0194

Cites

28 of 28 references verified0 citation errors · 0 not checkable

Statistics

Figures

FIG. 1. In 3 days of HFD, body weight, fat mass, and adipocyte size are increased significantly. Eight-week-old C57BL6J male mice were fed NCD until they were subjected to 60% HFD. HFD was treated to the mice 0 (NCD), 3 days (3 D), 1 week (1 W), 2 weeks (2 W), 5 weeks (5 W), or 10 weeks (10 W) before death. At the age of 18 weeks, all mice were killed and subjected to several analyses. A: Body weight of the mice at the end of the experiment. n = 8 at each time point. Increase of body weight started to be observed by 3 days of HFD. Body weight of mice with 5-week HFD and 10-week HFD was not significantly different. **P < 0.05. B: Epididymal (Epid.) fat mass. n = 8 at each time point. **P < 0.05; ***P < 0.001. C: Histology analysis of epididymal adipose tissue. The epididymal adipose tissues were subjected to hematoxylin-eosin staining. n = 4 at each time point. D and E: Further qualitative changes of adipocyte size and morphology by short-term HFD were assessed by histology analysis of whole-mount epididymal adipose tissue. D: BODIPY (boron-dipyrromethene) staining of whole-mount adipose tissue from the mice treated with NCD or HFD. Adipocyte size was markedly increased by 3 days of HFD. n = 6. Signal intensity of BODIPY staining was adjusted for optimal measurement of adipocyte size using ImageJ software. E: Distribution of adipocyte size in epididymal adipose tissue from mice treated with NCD or HFD. (A high-quality digital representation of this figure is available in the online issue.)
FIG. 1. In 3 days of HFD, body weight, fat mass, and adipocyte size are increased significantly. Eight-week-old C57BL6J male mice were fed NCD until they were subjected to 60% HFD. HFD was treated to the mice 0 (NCD), 3 days (3 D), 1 week (1 W), 2 weeks (2 W), 5 weeks (5 W), or 10 weeks (10 W) before death. At the age of 18 weeks, all mice were killed and subjected to several analyses. A: Body weight of the mice at the end of the experiment. n = 8 at each time point. Increase of body weight started to be observed by 3 days of HFD. Body weight of mice with 5-week HFD and 10-week HFD was not significantly different. **P < 0.05. B: Epididymal (Epid.) fat mass. n = 8 at each time point. **P < 0.05; ***P < 0.001. C: Histology analysis of epididymal adipose tissue. The epididymal adipose tissues were subjected to hematoxylin-eosin staining. n = 4 at each time point. D and E: Further qualitative changes of adipocyte size and morphology by short-term HFD were assessed by histology analysis of whole-mount epididymal adipose tissue. D: BODIPY (boron-dipyrromethene) staining of whole-mount adipose tissue from the mice treated with NCD or HFD. Adipocyte size was markedly increased by 3 days of HFD. n = 6. Signal intensity of BODIPY staining was adjusted for optimal measurement of adipocyte size using ImageJ software. E: Distribution of adipocyte size in epididymal adipose tissue from mice treated with NCD or HFD. (A high-quality digital representation of this figure is available in the online issue.)CC BY-NC-ND · PubMed Central
FIG. 2. HFD induces systemic insulin resistance in 3 days. A: C57BL/6J male mice were treated with NCD or HFD and subjected to oral glucose (Glc) tolerance test. n = 8 at each time point. ***P < 0.001 NCD vs. 3-day HFD. B: Blood insulin levels at time 0 and 10 min after glucose injection. Basal insulin level was significantly elevated by 3 days of HFD and then further increase was detected significantly by 5 and 10 weeks of HFD. n = 8. *P < 0.05 NCD vs. 3-day HFD; ***P < 0.001 NCD vs. 3-day HFD; †P < 0.05 3-day HFD vs. 10-week HFD; ††P < 0.01 3-day HFD vs. 10-week HFD. C–H: Hyperinsulinemic-euglycemic clamp was performed in mice treated with HFD for different periods; n = 8 (NCD, and 3-day and 1-week HFD mice) or n = 6 (10-week HFD mice). C: Basal blood glucose level (before clamp). **P < 0.01. D: Basal hepatic glucose production. *P < 0.05; **P < 0.01. E: GIR. **P < 0.01. F: ISGDR. **P < 0.01. G: Insulin-dependent suppression of hepatic glucose. **P < 0.01. H: Suppression of plasma FFA level by insulin. *P < 0.05; **P < 0.01.
FIG. 2. HFD induces systemic insulin resistance in 3 days. A: C57BL/6J male mice were treated with NCD or HFD and subjected to oral glucose (Glc) tolerance test. n = 8 at each time point. ***P < 0.001 NCD vs. 3-day HFD. B: Blood insulin levels at time 0 and 10 min after glucose injection. Basal insulin level was significantly elevated by 3 days of HFD and then further increase was detected significantly by 5 and 10 weeks of HFD. n = 8. *P < 0.05 NCD vs. 3-day HFD; ***P < 0.001 NCD vs. 3-day HFD; †P < 0.05 3-day HFD vs. 10-week HFD; ††P < 0.01 3-day HFD vs. 10-week HFD. C–H: Hyperinsulinemic-euglycemic clamp was performed in mice treated with HFD for different periods; n = 8 (NCD, and 3-day and 1-week HFD mice) or n = 6 (10-week HFD mice). C: Basal blood glucose level (before clamp). **P < 0.01. D: Basal hepatic glucose production. *P < 0.05; **P < 0.01. E: GIR. **P < 0.01. F: ISGDR. **P < 0.01. G: Insulin-dependent suppression of hepatic glucose. **P < 0.01. H: Suppression of plasma FFA level by insulin. *P < 0.05; **P < 0.01.CC BY-NC-ND · PubMed Central
FIG. 3. Macrophage (MP) infiltration and polarization increase in 3 days of HFD. Mice were treated with NCD (N) or HFD for a series of periods as indicated: 3D, 3 days; 2W, 2 weeks; 10W, 10 weeks. After 10 weeks from when first mice were fed an HFD, mice were killed and epididymal adipose tissues were taken for further analyses. A: Flow cytometry analyses of immune cells in stromal vascular fraction of adipose tissue. #P < 0.05; ##P < 0.01; ###P < 0.001; n = 4 (NCD and 2-week HFD mice) or n = 6 (1-week and 10-week HFD mice). B: Immunohistochemistry analysis of epididymal adipose tissue. The epididymal adipose tissues were stained with antibodies against MAC2 and then subjected to hematoxylin-eosin staining. n = 4. C: Whole-mount immunohistochemistry analysis of epididymal adipose tissue from NCD or 3- or 7-day HFD-treated mice. Samples were stained with DAPI (blue) or antibodies against CD11b (red) and CD11c (green) and visualized by multiphoton confocal microscopy. Scale bar denotes 50 μm. (A high-quality digital representation of this figure is available in the online issue.)
FIG. 3. Macrophage (MP) infiltration and polarization increase in 3 days of HFD. Mice were treated with NCD (N) or HFD for a series of periods as indicated: 3D, 3 days; 2W, 2 weeks; 10W, 10 weeks. After 10 weeks from when first mice were fed an HFD, mice were killed and epididymal adipose tissues were taken for further analyses. A: Flow cytometry analyses of immune cells in stromal vascular fraction of adipose tissue. #P < 0.05; ##P < 0.01; ###P < 0.001; n = 4 (NCD and 2-week HFD mice) or n = 6 (1-week and 10-week HFD mice). B: Immunohistochemistry analysis of epididymal adipose tissue. The epididymal adipose tissues were stained with antibodies against MAC2 and then subjected to hematoxylin-eosin staining. n = 4. C: Whole-mount immunohistochemistry analysis of epididymal adipose tissue from NCD or 3- or 7-day HFD-treated mice. Samples were stained with DAPI (blue) or antibodies against CD11b (red) and CD11c (green) and visualized by multiphoton confocal microscopy. Scale bar denotes 50 μm. (A high-quality digital representation of this figure is available in the online issue.)CC BY-NC-ND · PubMed Central
FIG. 4. Inflammatory gene expression is induced in 3 days after HFD. C57BL/6J mice were treated with an HFD. Mice were fed an HFD for 0 (0 or N [NCD]), 1 (1), 3 (3), or 7 days (7), or 16 weeks (H). mRNA levels of inflammatory genes from epididymal adipose tissue (WAT), brown adipose tissue (BAT), liver, and skeletal muscle were measured by quantitative real-time RT-PCR analysis. n = 10 at each time point. *P < 0.05; **P < 0.01; ***P < 0.001. iNOS, inducible nitric oxide synthase; SAA3, serum amyloid A3.
FIG. 4. Inflammatory gene expression is induced in 3 days after HFD. C57BL/6J mice were treated with an HFD. Mice were fed an HFD for 0 (0 or N [NCD]), 1 (1), 3 (3), or 7 days (7), or 16 weeks (H). mRNA levels of inflammatory genes from epididymal adipose tissue (WAT), brown adipose tissue (BAT), liver, and skeletal muscle were measured by quantitative real-time RT-PCR analysis. n = 10 at each time point. *P < 0.05; **P < 0.01; ***P < 0.001. iNOS, inducible nitric oxide synthase; SAA3, serum amyloid A3.CC BY-NC-ND · PubMed Central
FIG. 5. Adipocytes become more chemoattractive to macrophages after 3 days of HFD. A: Macrophage migration assays using primary ACM from mice treated with NCD (N) or HFD. ACM were obtained by incubating mouse primary adipocytes in serum-free Dulbecco’s modified Eagle’s medium for 12 h. 3d, 3 days; 1w, 1 week. B: MCP-1 protein expression from the primary adipocytes. C: MCP-1 protein secretion from those adipocytes. *P < 0.05; **P < 0.01.
FIG. 5. Adipocytes become more chemoattractive to macrophages after 3 days of HFD. A: Macrophage migration assays using primary ACM from mice treated with NCD (N) or HFD. ACM were obtained by incubating mouse primary adipocytes in serum-free Dulbecco’s modified Eagle’s medium for 12 h. 3d, 3 days; 1w, 1 week. B: MCP-1 protein expression from the primary adipocytes. C: MCP-1 protein secretion from those adipocytes. *P < 0.05; **P < 0.01.CC BY-NC-ND · PubMed Central
FIG. 6. Rag1 KO mice develop insulin resistance with increased macrophage activation in 1 week of HFD. A: Macrophage infiltration and M1 polarization were increased by short-term HFD. Rag1 KO mice were treated with HFD for 1 week and killed, and epididymal adipose tissues were taken for further analyses. Total macrophages (double positive; F4/80+, CD11b+) and CD11c+ macrophages (triple positive cells; F4/80+, CD11b+, CD11c+) were increased in adipose tissue in 1 week of HFD. *P < 0.05 KO-NCD vs. KO HFD; ***P < 0.001 KO-NCD vs. KO HFD; #P < 0.05 wild-type (WT)-NCD vs. WT HFD; ##P < 0.01 WT-NCD vs. WT HFD. n = 6. B: Epididymal (Epid.) adipose tissue mass in NCD and 1-week HFD-treated Rag1 KO mice. C: Expression of inflammatory genes was promoted in 1-week HFD-fed Rag1 KO mice. mRNA levels of inflammatory genes from epididymal adipose tissue were measured by quantitative real-time RT-PCR analysis. D–F: HFD rapidly induces systemic insulin resistance in Rag1 KO mice. D: Rag1 KO mice (8 weeks old, male) were treated with NCD or HFD for 3 days (3d) (i) or 1 week (1w) (ii) and subjected to oral glucose (Glc) tolerance test. E: Serum insulin levels of Rag1 KO mice treated with NCD or HFD (for 1 week) during oral glucose tolerance. 0 min, before glucose injection; 10 min, 10 min after glucose injection. F: WT or Rag1 KO mice were treated with NCD or HFD for 1 week and subjected to insulin tolerance test with intraperitoneal injection of insulin (IP-ITT). Blood glucose levels were measured at 0, 30, 60, 90, and 120 min after insulin (0.4 unit/kg) injection. G: Glucose-uptake assays using primary adipocytes from mice treated with NCD or HFD for 1 week. iNOS, inducible nitric oxide synthase; SAA3, serum amyloid A3. *P < 0.05; **P < 0.01; ***P < 0.001.
FIG. 6. Rag1 KO mice develop insulin resistance with increased macrophage activation in 1 week of HFD. A: Macrophage infiltration and M1 polarization were increased by short-term HFD. Rag1 KO mice were treated with HFD for 1 week and killed, and epididymal adipose tissues were taken for further analyses. Total macrophages (double positive; F4/80+, CD11b+) and CD11c+ macrophages (triple positive cells; F4/80+, CD11b+, CD11c+) were increased in adipose tissue in 1 week of HFD. *P < 0.05 KO-NCD vs. KO HFD; ***P < 0.001 KO-NCD vs. KO HFD; #P < 0.05 wild-type (WT)-NCD vs. WT HFD; ##P < 0.01 WT-NCD vs. WT HFD. n = 6. B: Epididymal (Epid.) adipose tissue mass in NCD and 1-week HFD-treated Rag1 KO mice. C: Expression of inflammatory genes was promoted in 1-week HFD-fed Rag1 KO mice. mRNA levels of inflammatory genes from epididymal adipose tissue were measured by quantitative real-time RT-PCR analysis. D–F: HFD rapidly induces systemic insulin resistance in Rag1 KO mice. D: Rag1 KO mice (8 weeks old, male) were treated with NCD or HFD for 3 days (3d) (i) or 1 week (1w) (ii) and subjected to oral glucose (Glc) tolerance test. E: Serum insulin levels of Rag1 KO mice treated with NCD or HFD (for 1 week) during oral glucose tolerance. 0 min, before glucose injection; 10 min, 10 min after glucose injection. F: WT or Rag1 KO mice were treated with NCD or HFD for 1 week and subjected to insulin tolerance test with intraperitoneal injection of insulin (IP-ITT). Blood glucose levels were measured at 0, 30, 60, 90, and 120 min after insulin (0.4 unit/kg) injection. G: Glucose-uptake assays using primary adipocytes from mice treated with NCD or HFD for 1 week. iNOS, inducible nitric oxide synthase; SAA3, serum amyloid A3. *P < 0.05; **P < 0.01; ***P < 0.001.CC BY-NC-ND · PubMed Central
FIG. 7. Macrophage depletion using clodronate-liposomes does not affect short-term HFD-dependent adipocyte insulin resistance. Mice were treated with NCD or 60% HFD in the presence or absence of clodronate injection. Mice were given clodronate injection (100 mg/kg i.p.) 3 days before HFD, which was followed by a second and third injection every 3 days (at days 0 and 3). A: Flow cytometry analysis of CD11c+ macrophages in adipose tissue. V, vehicle (empty liposomes); C, clodronate-liposomes. B: Whole-mount immunohistochemistry analysis of epididymal adipose tissue. Veh, vehicle; Clod, clodronate-liposomes. C: Cytokine concentration in the mouse sera injected with vehicle and clodronate. W, week. *P < 0.05. D: Glucose-uptake assays using primary adipocytes from mice treated with NCD or HFD for 1 week with or without clodronate injection. White columns denote relative glucose uptake activity without insulin. Black columns denote relative glucose uptake activity with insulin. Cld, clodronate-liposomes. E: Oral glucose tolerance test (OGTT) of mice treated with HFD for 3 days. #P < 0.05 Veh-NCD vs. Veh-HFD; *P < 0.05 Cld-NCD vs. Cld-HFD; **P < 0.01 Cld-NCD vs. Cld-HFD; ***P < 0.001 Cld-NCD vs. Cld-HFD. n = 6. F: Glucose tolerance test of mice treated with HFD for 7 days. #P < 0.05 Veh-NCD vs. Veh-HFD; ##P < 0.01 Veh-NCD vs. Veh-HFD; ###P < 0.001 Veh-NCD vs. Veh-HFD; *P < 0.05 Cld-NCD vs. Cld-HFD; **P < 0.01 Cld-NCD vs. Cld-HFD. n = 6. G: Homeostasis model assessment of insulin resistance (HOMA-IR). H–J: Hematopoietic cell-specific JNK deficiency does not affect short-term HFD-induced insulin resistance. For the generation of radiation chimera, C57BL/6J mice received a lethal dose of 10 Gy of ionizing radiation, followed by tail vein injection of 107 bone marrow cells either from wild-type (WT) or JNK KO mice. After 6 weeks of bone marrow reconstitution, mice were subjected to 3 or 7 days of HFD, followed by hyperinsulinemic-euglycemic clamp. n = 4 to 5. H: GIR. I: ISGDR. J: Insulin-dependent hepatic glucose suppression. BMT, bone marrow transplantation. (A high-quality digital representation of this figure is available in the online issue.)
FIG. 7. Macrophage depletion using clodronate-liposomes does not affect short-term HFD-dependent adipocyte insulin resistance. Mice were treated with NCD or 60% HFD in the presence or absence of clodronate injection. Mice were given clodronate injection (100 mg/kg i.p.) 3 days before HFD, which was followed by a second and third injection every 3 days (at days 0 and 3). A: Flow cytometry analysis of CD11c+ macrophages in adipose tissue. V, vehicle (empty liposomes); C, clodronate-liposomes. B: Whole-mount immunohistochemistry analysis of epididymal adipose tissue. Veh, vehicle; Clod, clodronate-liposomes. C: Cytokine concentration in the mouse sera injected with vehicle and clodronate. W, week. *P < 0.05. D: Glucose-uptake assays using primary adipocytes from mice treated with NCD or HFD for 1 week with or without clodronate injection. White columns denote relative glucose uptake activity without insulin. Black columns denote relative glucose uptake activity with insulin. Cld, clodronate-liposomes. E: Oral glucose tolerance test (OGTT) of mice treated with HFD for 3 days. #P < 0.05 Veh-NCD vs. Veh-HFD; *P < 0.05 Cld-NCD vs. Cld-HFD; **P < 0.01 Cld-NCD vs. Cld-HFD; ***P < 0.001 Cld-NCD vs. Cld-HFD. n = 6. F: Glucose tolerance test of mice treated with HFD for 7 days. #P < 0.05 Veh-NCD vs. Veh-HFD; ##P < 0.01 Veh-NCD vs. Veh-HFD; ###P < 0.001 Veh-NCD vs. Veh-HFD; *P < 0.05 Cld-NCD vs. Cld-HFD; **P < 0.01 Cld-NCD vs. Cld-HFD. n = 6. G: Homeostasis model assessment of insulin resistance (HOMA-IR). H–J: Hematopoietic cell-specific JNK deficiency does not affect short-term HFD-induced insulin resistance. For the generation of radiation chimera, C57BL/6J mice received a lethal dose of 10 Gy of ionizing radiation, followed by tail vein injection of 107 bone marrow cells either from wild-type (WT) or JNK KO mice. After 6 weeks of bone marrow reconstitution, mice were subjected to 3 or 7 days of HFD, followed by hyperinsulinemic-euglycemic clamp. n = 4 to 5. H: GIR. I: ISGDR. J: Insulin-dependent hepatic glucose suppression. BMT, bone marrow transplantation. (A high-quality digital representation of this figure is available in the online issue.)CC BY-NC-ND · PubMed Central
FIG. 8. Lipid contents of liver and skeletal muscle after 3 days of HFD. Eighteen-week-old C57BL6J male chow-fed mice were started in 60% HFD at day 0 for 3 days before the analyses. A separate group of age-matched chow-fed mice was studied as controls. For the macrophage depletion experiment, two shots of clodronate injection (100 mg/kg i.p.) were given at day −3 and 0. Veh, vehicle; Clod, clodronate-liposomes; TG, triacylglyceride; NS, not significant. A: Lipid contents in liver. B: Lipid contents in skeletal muscle. n = 8. *P < 0.05; **P < 0.01.
FIG. 8. Lipid contents of liver and skeletal muscle after 3 days of HFD. Eighteen-week-old C57BL6J male chow-fed mice were started in 60% HFD at day 0 for 3 days before the analyses. A separate group of age-matched chow-fed mice was studied as controls. For the macrophage depletion experiment, two shots of clodronate injection (100 mg/kg i.p.) were given at day −3 and 0. Veh, vehicle; Clod, clodronate-liposomes; TG, triacylglyceride; NS, not significant. A: Lipid contents in liver. B: Lipid contents in skeletal muscle. n = 8. *P < 0.05; **P < 0.01.CC BY-NC-ND · PubMed Central

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Show all 28 references

Cited by

Sorted by citations

Items 401–500 of 564

Related

See all

Metadata

Authors
Lee, Y. S., Li, P., Huh, J. Y., Hwang, I. J., Lu, M., Kim, J. I., Ham, M., Talukdar, S., Chen, A., Lu, W. J., Bandyopadhyay, G. K., Schwendener, R., Olefsky, J., & Kim, J. B.
Affiliations
  • Seoul National University (KR)
  • University of California San Diego (US)
  • Institute of Molecular Biology and Genetics, Seoul National University, Seoul, Korea
  • University of Zurich (CH)
Corresponding author
Kim, Jae Bum
ORCID
Venue
Diabetes
Publisher
American Diabetes Association
Published
2011-09-16
Volume
60
Issue
10
Pages
2474-2483
ISSN
  • 0012-1797 (ISSN-L)
  • 1939-327X
DOI
10.2337/db11-0194
PMC
PMC3178297
OpenAlex
W2095717717
Cited by
566
References
28
Citations by year
2026: 24 · 2025: 23 · 2024: 26 · 2023: 33 · 2022: 40 · 2021: 41 · 2020: 44 · 2019: 47 · 2018: 53 · 2017: 50 · 2016: 37 · 2015: 46 · 2014: 24 · 2013: 49 · 2012: 23
FWCI
24.10
Type
journal article
Language
en
Open access
Licence
Locations
  • Diabetes (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, cc-by)
  • Zurich Open Repository and Archive (University of Zurich) (submittedVersion, cc-by)
  • Zurich Open Repository and Archive (University of Zurich)
Funders
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK063491, DK 074868, DK 033651, T32DK007494, R37DK033651, P01DK074868, R01DK033651, P30DK063491)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (P50HD012303, U54HD012303)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
  • Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
Keywords
insulin resistance, high-fat diet, inflammation, obesity, macrophages, adipose tissue, Rag1 knockout mice, macrophage depletion, lipid accumulation, hepatic lipid accumulation, skeletal muscle lipid accumulation
MeSH terms
Adipose Tissue, Animals, Blood Glucose, Ceramides, Dietary Fats, Drug Administration Schedule, Epididymis, Glucose, Glucose Tolerance Test, Inflammation, Insulin Resistance, Liver, Male, Mice, Inbred C57BL, Muscle, Skeletal, Mice

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review