An Hsp20-FBXO4 Axis Regulates Adipocyte Function through Modulating PPARγ Ubiquitination

Abstract

SUMMARY Exposure to cold temperature is well known to upregulate heat shock protein (Hsp) expression and recruit and/or activate brown adipose tissue and beige adipocytes in humans and animals. However, whether and how Hsps regulate adipocyte function for energy homeostatic responses is poorly understood. Here, we demonstrate a critical role of Hsp20 as a negative regulator of adipocyte function. Deletion of Hsp20 enhances non-shivering thermogenesis and suppresses inflammatory responses, leading to improvement of glucose and lipid metabolism under both chow diet and high-fat diet conditions. Mechanistically, Hsp20 controls adipocyte function by interacting with the subunit of the ubiquitin ligase complex, F-box only protein 4 (FBXO4), and regulating the ubiquitin-dependent degradation of peroxisome proliferation activated receptor gamma (PPARγ). Indeed, Hsp20 deficiency mimics and enhances the pharmacological effects of the PPARγ agonist rosiglitazone. Together, our findings suggest a role of Hsp20 in mediating adipocyte function by linking β-adrenergic signaling to PPARγ activity.

GDF3 Protects Mice against Sepsis-Induced Cardiac Dysfunction and Mortality by Suppression of Macrophage Pro-Inflammatory Phenotype

“…Flow cytometry analysis was performed by the standard method, as previously described [15,16] via an LSR II flow cytometer unit (BD Biosciences, San Jose, CA, USA). Briefly, mice were euthanized and perfused with 10 mL PBS via left ventricle to remove circulating immune cells; then heart tissue was isolated and minced into small pieces, followed by digestion with HBSS with Collagenase IV (2 mg/mL, #LS004188, Worthington Biochemical Co., Lakewood, NJ, USA), Dispase II (1.2 U/mL, #D4693, Sigma) and 0.9 mM CaCl 2 , then incubated at 37 • C for 45 min with gentle agitation.…”

Tumor susceptibility gene 101 ameliorates endotoxin-induced cardiac dysfunction by enhancing Parkin-mediated mitophagy

“…The concentrations of total, cytosolic, and mitochondrial protein were determined by protein assay reagent (Bio-Rad). Samples (25-100 g) were loaded to SDS-PAGE as discussed in detail elsewhere (45). The dilutions and sources of the primary antibodies used in this study were as follows: mouse anti-TSG101 (Santa Cruz, 1:1000), PINK1 (Cell Signaling, 1:1000), Parkin (Cell Signaling, 1:1000), LC3 (Cell Signaling, 1:500), Mfn1 (Abcam, 1:1000), Mfn2 (Abcam, 1:1000), Drp1 (Cell Signaling, 1:500), and PGC-1a (Proteintech, 1:1000).…”

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