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Rnf20 deficiency in adipocyte impairs adipose tissue development and thermogenesis.

ABSTRACT: RNF20, an E3 ligase critical for monoubiquitination of histone H2B at lysine 120 (H2Bub), has been implicated in the regulation of various cellar processes; however, its physiological roles in adipocytes remain poorly characterized. Here, we report that the adipocyte-specific knockout of Rnf20 (ASKO) in mice led to progressive fat loss, organomegaly and hyperinsulinemia. Despite signs of hyperinsulinemia, normal insulin sensitivity and improved glucose tolerance were observed in the young and aged CD-fed ASKO mice. In addition, high-fat diet-fed ASKO mice developed severe liver steatosis. Moreover, we observed that the ASKO mice were extremely sensitive to a cold environment due to decreased expression levels of brown adipose tissue (BAT) selective genes, including uncoupling protein 1 (Ucp1), and impaired mitochondrial functions. Significantly decreased levels of peroxisome proliferator-activated receptor gamma (Pparγ) were observed in the gonadal white adipose tissues (gWAT) from the ASKO mice, suggesting that Rnf20 regulates adipogenesis, at least in part, through Pparγ. Rosiglitazone-treated ASKO mice exhibited increased fat mass compared to that of the non-treated ASKO mice. Collectively, our results illustrate the critical role of RNF20 in control of white and brown adipose tissue development and physiological function.

SUBMITTER: Liang X

PROVIDER: S-EPMC8160045 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Corin Deficiency Alters Adipose Tissue Phenotype and Impairs Thermogenesis in Mice.

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Brown Adipocyte-Specific PPAR? (Peroxisome Proliferator-Activated Receptor ?) Deletion Impairs Perivascular Adipose Tissue Development and Enhances Atherosclerosis in Mice.

Project description:Objective- Perivascular adipose tissue (PVAT) contributes to vascular homeostasis by producing paracrine factors. Previously, we reported that selective deletion of PPAR? (peroxisome proliferator-activated receptor ?) in vascular smooth muscle cells resulted in concurrent loss of PVAT and enhanced atherosclerosis in mice. To address the causal relationship between loss of PVAT and atherosclerosis, we used BA-PPAR?-KO (brown adipocyte-specific PPAR? knockout) mice. Approach and Results- Deletion of PPAR? in brown adipocytes did not affect PPAR? in white adipocytes or vascular smooth muscle cells or PPAR? and PPAR? expression in brown adipocytes. However, development of PVAT and interscapular brown adipose tissue was remarkably impaired, associated with reduced expression of genes encoding lipogenic enzymes in the BA-PPAR?-KO mice. Thermogenesis in brown adipose tissue was significantly impaired with reduced expression of thermogenesis genes in brown adipose tissue and compensatory increase in subcutaneous and gonadal white adipose tissues. Remarkably, basal expression of inflammatory genes and macrophage infiltration in PVAT and brown adipose tissue were significantly increased in the BA-PPAR?-KO mice. BA-PPAR?-KO mice were crossbred with ApoE KO (apolipoprotein E knockout) mice to investigate the development of atherosclerosis. Flow cytometry analysis confirmed increased systemic and PVAT inflammation. Consequently, atherosclerotic lesions were significantly increased in mice with impaired PVAT development, thus indicating that the lack of normal PVAT is sufficient to drive increased atherosclerosis. Conclusions- PPAR? is required for functional PVAT development. PPAR? deficiency in PVAT, while still expressed in vascular smooth muscle cell, enhances atherosclerosis and results in vascular and systemic inflammation, providing new insights on the specific roles of PVAT in atherosclerosis and cardiovascular disease at large.

| S-EPMC6202167 | biostudies-literature

Loss of Adipose Growth Hormone Receptor in Mice Enhances Local Fatty Acid Trapping and Impairs Brown Adipose Tissue Thermogenesis.

Project description:Growth hormone (GH) binds to its receptor (growth hormone receptor [GHR]) to exert its pleiotropic effects on growth and metabolism. Disrupted GH/GHR actions not only fail growth but also are involved in many metabolic disorders, as shown in murine models with global or tissue-specific Ghr deficiency and clinical observations. Here we constructed an adipose-specific Ghr knockout mouse model Ad-GHRKO and studied the metabolic adaptability of the mice when stressed by high-fat diet (HFD) or cold. We found that disruption of adipose Ghr accelerated dietary obesity but protected the liver from ectopic adiposity through free fatty acid trapping. The heat-producing brown adipose tissue burning and white adipose tissue browning induced by cold were slowed in the absence of adipose Ghr but were recovered after prolonged cold acclimation. We conclude that at the expense of excessive subcutaneous fat accumulation and lower emergent cold tolerance, down-tuning adipose GHR signaling emulates a healthy obesity situation which has metabolic advantages against HFD.

| S-EPMC6545351 | biostudies-literature

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