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

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

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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

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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.

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Background
Insulin Resistance in the Defense against Obesity
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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: Lee, Yun Sok
Li, Pingping
Huh, Jin Young
Lu, Min
Kim, Jong In
Ham, Mira
Talukdar, Saswata
Schwendener, Reto
Olefsky, Jerrold
Kim, Jae Bum
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: hybrid
doi.org
Licence: cc-by-nc-nd
creativecommons.org/licenses/by-nc-nd/3.0/ (vor, 3636 d)
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

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

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