The DOI matches its Crossref record; 38 of the 38 references it cites were found in a registry or an index.
The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity
Abstract
Adiponectin is an adipocyte-derived hormone. Recent genome-wide scans have mapped a susceptibility locus for type 2 diabetes and metabolic syndrome to chromosome 3q27, where the gene encoding adiponectin is located. Here we show that decreased expression of adiponectin correlates with insulin resistance in mouse models of altered insulin sensitivity. Adiponectin decreases insulin resistance by decreasing triglyceride content in muscle and liver in obese mice. This effect results from increased expression of molecules involved in both fatty-acid combustion and energy dissipation in muscle. Moreover, insulin resistance in lipoatrophic mice was completely reversed by the combination of physiological doses of adiponectin and leptin, but only partially by either adiponectin or leptin alone. We conclude that decreased adiponectin is implicated in the development of insulin resistance in mouse models of both obesity and lipoatrophy. These data also indicate that the replenishment of adiponectin might provide a novel treatment modality for insulin resistance and type 2 diabetes.
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In the citing paper
“Increases in adiponectin have been demonstrated to improve insulin sensitivity through insulin-sensitizing effects in mice [20].”
From Tirzepatide as monotherapy improved markers of beta-cell function and insulin sensitivity in type 2 diabetes (SURPASS-1). (2023) · cites this paper as [20]
In the citing paper
“Adiponectin is exclusively produced in adipocytes, and adiponectin levels are lower in T2D and obesity compared to the healthy state [20, 21].”
From Tirzepatide as monotherapy improved markers of beta-cell function and insulin sensitivity in type 2 diabetes (SURPASS-1). (2023) · cites this paper as [20]
In the citing paper
“(v) in rodents, injection of recombinant adiponectin increases fat oxidation, reduces intamyocellular lipid, and improves insulin sensitivity [77];”
From Pathogenesis of insulin resistance in skeletal muscle (2010) · cites this paper as [77]
In the citing paper
“High-fat diet-induced obesity leads to reduced expression of ApN, thereby causing insulin resistance [47].”
From Adiponectin and Its Mimics on Skeletal Muscle: Insulin Sensitizers, Fat Burners, Exercise Mimickers, Muscling Pills … or Everything Together? (2020) · cites this paper as [47]
In the citing paper
“Administration of ApN lowered blood sugar and reduced insulin resistance in mice under a high-fat diet (HFD) [47].”
From Adiponectin and Its Mimics on Skeletal Muscle: Insulin Sensitizers, Fat Burners, Exercise Mimickers, Muscling Pills … or Everything Together? (2020) · cites this paper as [47]
In the citing paper
“Adiponectin administration decreases IHTG (35), increases hepatic insulin sensitivity (36), and reverses obesity-related skeletal muscle insulin resistance (37).”
From Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity (2009) · cites this paper as [37]
In the citing paper
“It is thought that adiponectin can decrease the insulin resistance of obesity (28–30).”
From Phenotypic effects of leptin replacement on morbid obesity, diabetes mellitus, hypogonadism, and behavior in leptin-deficient adults (2004) · cites this paper as [30]
In the citing paper
“Likewise, in one animal model, leptin alone produced a near-maximal effect (35), whereas a second model demonstrated a synergistic effect with adiponectin (33).”
From Long-Term Efficacy of Leptin Replacement in Patients With Generalized Lipodystrophy (2005) · cites this paper as [33]
In the citing paper
“Adiponectin is another adipokine that is associated with increased insulin sensitivity and fatty acid oxidation (33).”
From Long-Term Efficacy of Leptin Replacement in Patients With Generalized Lipodystrophy (2005) · cites this paper as [33]
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Metadata
- Authors
- Yamauchi, T., Kamon, J., Waki, H., Terauchi, Y., Kubota, N., Hara, K., Mori, Y., Ide, T., Murakami, K., Tsuboyama-Kasaoka, N., Ezaki, O., Akanuma, Y., Gavrilova, O., Vinson, C., Reitman, M. L., Kagechika, H., Shudo, K., Yoda, M., Nakano, Y., Tobe, K., Nagai, R., Kimura, S., Tomita, M., Froguel, P., & Kadowaki, T.
- Affiliations
- The University of Tokyo (JP)
- Centre National de la Recherche Scientifique (FR)
- National Institute of Health and Nutrition (JP)
- National Institute of Diabetes and Digestive and Kidney Diseases (US)
- National Institutes of Health (US)
- SHOWA Medical University (JP)
- Corresponding author
- Kadowaki, T.
- ORCID
- Venue
- Nature Medicine
- Published
- 2001-08
- Volume
- 7
- Issue
- 8
- Pages
- 941-946
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W1587875569
- Cited by
- 4,915
- References
- 38
- Citations by year
- 2026: 48 · 2025: 75 · 2024: 100 · 2023: 127 · 2022: 125 · 2021: 127 · 2020: 214 · 2019: 168 · 2018: 152 · 2017: 157 · 2016: 203 · 2015: 208 · 2014: 198 · 2013: 258 · 2012: 229
- FWCI
- 160.38
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- adiponectin, insulin resistance, lipoatrophy, obesity, type 2 diabetes, leptin, triglyceride content, muscle, liver, fatty acid oxidation, energy dissipation, chromosome 3q27, metabolic syndrome, adipokines
- MeSH terms
- Adipose Tissue, Amino Acid Sequence, Animals, Insulin Resistance, Molecular Sequence Data, Obesity, Oxidation-Reduction, Proteins, Transcription Factors, Triglycerides, Signal Transduction, Receptors, Cytoplasmic and Nuclear, Leptin, Intercellular Signaling Peptides and Proteins, Mice, Adiponectin
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