Rutin Maintains the Thermogenic Phenotype of Beige Adipocytes and Concomitantly Suppresses Mitophagy Against Obesity in HFD Mice

TL;DR

Rutin helps maintain the heat-producing function of beige fat cells and reduces obesity in mice fed a high-fat diet.

Contribution

Rutin prevents beige adipocyte reversion to white adipocytes and suppresses mitophagy in a high-fat diet-induced obesity model.

Findings

Rutin ameliorates metabolic disorders and prevents adipose tissue expansion in HFD mice.

Rutin suppresses mitochondrial autophagy and upregulates thermogenic markers in beige adipocytes.

Rutin sustains mitochondrial function and thermogenic phenotype in beige adipocytes under HFD conditions.

Abstract

Background: The browning of white adipose tissue for thermogenesis is an effective strategy for combating obesity. The formation of beige adipocytes is reversible, making their maintenance a key therapeutic target. Rutin has been shown to promote the transition from white to beige adipocytes. It remains unclear whether rutin can prevent the reversion of beige adipocytes to white adipocytes and what mechanisms underlie this process. Objectives: This study aims to determine whether rutin can sustain the thermogenic phenotype of beige adipocytes and to elucidate its mechanism. Methods: We established a beige adipocyte model with CL-316, 243(CL) in vitro. A white adipocyte model was created by CL withdrawal after 3 days. Then, we conducted a co-intervention with CL and rutin, as well as sustained rutin intervention on beige adipocytes following CL withdrawal. In vivo, we utilized a C57BL/6 mouse model, including ND, high-fat diet (HFD), and HFD + Rutin groups. The mice were further divided into Cold and −Cold groups, with the former undergoing 7 days of exposure to 4 °C and the latter experiencing 10 days of 22–24 °C. Rutin was administered continuously until the conclusion of the experiment. Results: Rutin consistently ameliorates metabolic disorders and prevents the expansion of adipose tissue. It concomitantly suppresses mitochondrial autophagy during beige induction, upregulates thermogenic markers in brown adipocytes, and safeguards the mitochondrial-related functional indicators. Conclusions: In summary, rutin obstructs the transformation of beige adipocytes into white adipocytes and concomitantly suppresses mitochondrial autophagy, thereby continuously improving obesity induced by a high-fat diet.

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