Cited by 911Adipokines, Inflammation, and Metabolic DiseasesAdipose Tissue and MetabolismRegulation of Appetite and Obesity

Globular adiponectin protected ob/ob mice from diabetes and ApoE-deficient mice from atherosclerosis

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Yamauchi, Toshimasa, Kamon, Junji, Waki, Hironori, Imai, Yasushi, Shimozawa, Nobuhiro, Hioki, Kyouji, Uchida, Shoko, Ito, Yusuke +16 more·2003·Journal of Biological Chemistry

Abstract

The adipocyte-derived hormone adiponectin has been shown to play important roles in the regulation of energy homeostasis and insulin sensitivity. In this study, we analyzed globular domain adiponectin (gAd) transgenic (Tg) mice crossed with leptin-deficient ob/ob or apoE-deficient mice. Interestingly, despite an unexpected similar body weight, gAd Tg ob/ob mice showed amelioration of insulin resistance and beta-cell degranulation as well as diabetes, indicating that globular adiponectin and leptin appeared to have both distinct and overlapping functions. Amelioration of diabetes and insulin resistance was associated with increased expression of molecules involved in fatty acid oxidation such as acyl-CoA oxidase, and molecules involved in energy dissipation such as uncoupling proteins 2 and 3 and increased fatty acid oxidation in skeletal muscle of gAd Tg ob/ob mice. Moreover, despite similar plasma glucose and lipid levels on an apoE-deficient background, gAd Tg apoE-deficient mice showed amelioration of atherosclerosis, which was associated with decreased expression of class A scavenger receptor and tumor necrosis factor alpha. This is the first demonstration that globular adiponectin can protect against atherosclerosis in vivo. In conclusion, replenishment of globular adiponectin may provide a novel treatment modality for both type 2 diabetes and atherosclerosis.

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Crossref · 10.1074/jbc.m209033200

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Authors
Yamauchi, T., Kamon, J., Waki, H., Imai, Y., Shimozawa, N., Hioki, K., Uchida, S., Ito, Y., Takakuwa, K., Matsui, J., Takata, M., Eto, K., Terauchi, Y., Komeda, K., Tsunoda, M., Murakami, K., Ohnishi, Y., Naitoh, T., Yamamura, K., Ueyama, Y., Froguel, P., Kimura, S., Nagai, R., & Kadowaki, T.
Affiliations
  • The University of Tokyo (JP)
  • Nissan Chemical Corporation (Japan) (JP)
  • Central Institute for Experimental Animals (JP)
  • Tokyo Medical University (JP)
  • Centre National de la Recherche Scientifique (FR)
Corresponding author
Kadowaki, Takashi
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2003-01
Volume
278
Issue
4
Pages
2461-2468
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2107865201
Cited by
911
References
33
Citations by year
2026: 4 · 2025: 10 · 2024: 12 · 2023: 10 · 2022: 22 · 2021: 22 · 2020: 19 · 2019: 18 · 2018: 15 · 2017: 25 · 2016: 38 · 2015: 40 · 2014: 38 · 2013: 51 · 2012: 48
FWCI
56.01
Type
journal article
Language
en
Open access
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
  • Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Keywords
globular adiponectin, adiponectin, ob/ob mice, leptin deficiency, type 2 diabetes, insulin resistance, beta cell degranulation, atherosclerosis, ApoE-deficient mice, fatty acid oxidation, acyl-CoA oxidase, uncoupling proteins, skeletal muscle, scavenger receptor A, TNF-α, transgenic mice
MeSH terms
Animals, Apolipoproteins E, Arteriosclerosis, Diabetes Mellitus, Dose-Response Relationship, Drug, Insulin, Insulin Resistance, Islets of Langerhans, Ligands, Male, Mice, Obese, Mice, Transgenic, Proteins, Risk Factors, Time Factors, Transcription Factors, Immunoblotting, Blotting, Northern, DNA, Complementary, Receptors, Cytoplasmic and Nuclear, Muscle, Skeletal, Intercellular Signaling Peptides and Proteins, Lipid Metabolism, Mice, Adiponectin

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