Disruption of Adiponectin Causes Insulin Resistance and Neointimal Formation*

By N. Kubota, Y. Terauchi, Toshimasa Yamauchi, Tetsuya Kubota, M. Moroi, J. Matsui, K. Eto, Tokuyuki Yamashita, J. Kamon, H. Satoh and 6 more. Journal of Biological Chemistry, 2002

1,411 citations recorded by the source corpus.

The adipocyte-derived hormone adiponectin has been proposed to play important roles in the regulation of energy homeostasis and insulin sensitivity, and it has been reported to exhibit putative antiatherogenic properties in vitro. In this study we generated adiponectin-deficient mice to directly investigate whether adiponectin has a physiological protective role against diabetes and atherosclerosis in vivo. Heterozygous adiponectin-deficient (adipo +/−) mice showed mild insulin resistance, while homozygous adiponectin-deficient (adipo −/−) mice showed moderate insulin resistance with glucose intolerance despite body weight gain similar to that of wild-type mice. Moreover, adipo −/−mice showed 2-fold more neointimal formation in response to external vascular cuff injury than wild-type mice (p = 0.01). This study provides the first direct evidence that adiponectin plays a protective role against insulin resistance and atherosclerosis in vivo.

Subfields: Cardiology and Cardiovascular Medicine, Endocrine and Autonomic Systems, Epidemiology

View Paper: https://www.semanticscholar.org/paper/1c780741753e8c82872704d87ddb817399bf7155

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Citations in the corpus

Plasma adiponectin concentrations predict insulin sensitivity of both glucose and lipid metabolism. (2003, background): “showing that administration of recombinant adiponectin increases insulin sensitivity in both lipotrophic and obese murine models of insulin resistance (11) and studies demonstrating reduced insulin sensitivity in the adiponectin knockout mice (12).”
The fat-derived hormone adiponectin alleviates alcoholic and nonalcoholic fatty liver diseases in mice. (2003, positive): “These direct antidiabetic and antiatherogenic actions have been further confirmed by two recent independent knockout studies that demonstrated that depletion of adiponectin induced insulin resistance as well as neointimal formation after vessel injury (19, 41).”
Regulation of energy metabolism by long-chain fatty acids. (2014, background): “Two independent studies showed that adiponectin KO mice when fed regular diet did not develop insulin resistance assessed by a glucose tolerance test and an insulin tolerance test [212,218] although another independent study reported development of mild insulin resistance [219].”
Obesity, Oxidative Stress, Adipose Tissue Dysfunction, and the Associated Health Risks: Causes and Therapeutic Strategies (2015, background): “A defect in insulin secretion has been observed in adiponectin knockout mice.(241) Globular domain adiponectin (gAd) is the functional adiponectin protein.”
Adipose tissue-derived factors: impact on health and disease. (2006, background): “cular injury (99, 138, 139); apolipoprotein E knockout mice”
Relationship of adiponectin to body fat distribution, insulin sensitivity and plasma lipoproteins: evidence for independent roles of age and sex (2003, background): “This finding is supported by studies in heterozygous and homozygous adiponectin null mice which showed a dose-dependent effect of adiponectin deficiency on insulin sensitivity [38].”
Inflammatory Mechanisms in the Regulation of Insulin Resistance (2008, background): “In other studies with adiponectin-deficient mice, however, these animals developed insulin resistance only if fed a high-fat diet (40) or failed to develop insulin resistance even when fed a high-fat diet (41).”
Adipocytes as regulators of energy balance and glucose homeostasis (2006, background): “Loss-of-function models of adiponectin have been more variable, with different groups reporting reduced insulin sensitivity on both chow and high-fat diets, high-fat diet only, or no effect on insulin action at al”
Induction of adiponectin, a fat-derived antidiabetic and antiatherogenic factor, by nuclear receptors. (2003, background): “Finally, adiponectin deficiency in knockout mice causes diet-induced insulin resistance and diabetes and increases neointimal thicking in the arterial wall by mechanic injury (20,26,27).”