Adipocyte-specific deletion of manganese superoxide dismutase protects from diet-induced obesity through increased mitochondrial uncoupling and biogenesis

Yong Hwan Han, Márcio Buffolo, Karla Maria Pires, Shaobo Pei, Philipp E. Scherer, Sihem Boudina

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Obesity and insulin resistance are associated with oxidative stress (OS). The causal role of adipose OS in the pathogenesis of these conditions is unknown. To address this issue, we generated mice with an adipocyte-selective deletion of manganese superoxide dismutase (MnSOD). When fed a high-fat diet (HFD), the AdSod2 knockout (KO) mice exhibited less adiposity, reduced adipocyte hypertrophy, and decreased circulating leptin. The resistance to diet-induced adiposity was the result of an increased metabolic rate and energy expenditure. Furthermore, palmitate oxidation was elevated in the white adipose tissue (WAT) and brown adipose tissue of AdSod2 KO mice fed an HFD, and the expression of key fatty acid oxidation genes was increased. To gain mechanistic insight into the increased fat oxidation in HFD-fed AdSod2 KO mice, we quantified the mitochondrial function and mitochondrial content in WAT and found that MnSOD deletion increased mitochondrial oxygen consumption and induced mitochondrial biogenesis. This effect was preserved in cultured adipocytes from AdSod2 KO mice in vitro. As expected from the enhanced fat oxidation, circulating levels of free fatty acids were reduced in the HFD-fed AdSod2 KO mice. Finally, HFD-fed AdSod2 KO mice were protected from hepatic steatosis, adipose tissue inflammation, and glucose and insulin intolerance. Taken together, these results demonstrate that MnSOD deletion in adipocytes triggered an adaptive stress response that activated mitochondrial biogenesis and enhanced mitochondrial fatty acid oxidation, thereby preventing diet-induced obesity and insulin resistance.

Original languageEnglish (US)
Pages (from-to)2639-2651
Number of pages13
JournalDiabetes
Volume65
Issue number9
DOIs
StatePublished - Sep 1 2016

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Organelle Biogenesis
Adipocytes
Knockout Mice
Superoxide Dismutase
High Fat Diet
Obesity
Diet
White Adipose Tissue
Adiposity
Insulin Resistance
Oxidative Stress
Fatty Acids
Fats
Brown Adipose Tissue
Glucose Intolerance
Palmitates
Leptin
Nonesterified Fatty Acids
Oxygen Consumption
Hypertrophy

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Adipocyte-specific deletion of manganese superoxide dismutase protects from diet-induced obesity through increased mitochondrial uncoupling and biogenesis. / Han, Yong Hwan; Buffolo, Márcio; Pires, Karla Maria; Pei, Shaobo; Scherer, Philipp E.; Boudina, Sihem.

In: Diabetes, Vol. 65, No. 9, 01.09.2016, p. 2639-2651.

Research output: Contribution to journalArticle

Han, Yong Hwan ; Buffolo, Márcio ; Pires, Karla Maria ; Pei, Shaobo ; Scherer, Philipp E. ; Boudina, Sihem. / Adipocyte-specific deletion of manganese superoxide dismutase protects from diet-induced obesity through increased mitochondrial uncoupling and biogenesis. In: Diabetes. 2016 ; Vol. 65, No. 9. pp. 2639-2651.
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