Tetraspanin7 in adipose tissue remodeling and its impact on metabolic health

IF 7 2区医学 Q1 ENDOCRINOLOGY & METABOLISM

Molecular Metabolism Pub Date : 2025-05-12 DOI:10.1016/j.molmet.2025.102168

Shino Nemoto , Kazuyo Uchida , Tetsuya Kubota , Manabu Nakayama , Yong-Woon Han , Shigeo Koyasu , Hiroshi Ohno

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引用次数: 0

Abstract

Objective

We previously identified tetraspanin 7 (Tspan7) as a candidate gene influencing body weight in an obesity-related gene screening study. However, the mechanisms underlying its involvement in body weight regulation remained unclear. This study aims to investigate the role of TSPAN7 from a metabolic perspective.

Methods

We utilized genetically modified mice, including adipose tissue-specific Tspan7-knockout and Tspan7-overexpressing models, as well as human adipose-derived stem cells with TSPAN7 knockdown and overexpression. Morphological, molecular, and omics analyses, including proteomics and transcriptomics, were performed to investigate TSPAN7 function. Physiological effects were assessed by measuring blood markers associated with lipid regulation under metabolic challenges, such as high-fat feeding and aging.

Results

We show that TSPAN7 is involved in regulating lipid droplet formation and stabilization. Tspan7-knockout mice exhibited an increased proportion of small-sized adipocytes and a reduced visceral-to-subcutaneous fat ratio. This shift in fat distribution was associated with improved insulin sensitivity and altered branched-chain amino acid metabolism, as evidenced by increased expression of the branched-chain α-keto acid dehydrogenase complex subunit B in Tspan7-modified mice. Mechanistically, TSPAN7 deficiency promoted subcutaneous fat expansion, alleviating metabolic stress on visceral fat, a major contributor to insulin resistance.

Conclusions

TSPAN7 influences lipid metabolism by modulating adipose tissue remodeling, particularly under metabolic challenges, such as high-fat diet exposure and aging. Its modulation enhances subcutaneous fat storage capacity while mitigating visceral fat accumulation, leading to improved insulin sensitivity. These findings position TSPAN7 as a potential target for therapeutic interventions aimed at improving metabolic health and preventing obesity-related diseases.

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Tetraspanin7在脂肪组织重塑及其对代谢健康的影响

目的：我们之前在一项肥胖相关基因筛选研究中确定了四跨蛋白7 （Tspan7）作为影响体重的候选基因。然而，其参与体重调节的机制尚不清楚。本研究旨在从代谢角度探讨TSPAN7的作用。方法：我们利用转基因小鼠，包括脂肪组织特异性TSPAN7敲除和TSPAN7过表达模型，以及TSPAN7敲除和过表达的人脂肪源性干细胞。形态学、分子和组学分析，包括蛋白质组学和转录组学，研究了TSPAN7的功能。通过测量代谢挑战（如高脂肪喂养和衰老）下与脂质调节相关的血液标志物来评估生理效应。结果：我们发现TSPAN7参与调节脂滴的形成和稳定。tspan7基因敲除小鼠表现出小尺寸脂肪细胞比例增加和内脏与皮下脂肪比例降低。这种脂肪分布的改变与胰岛素敏感性的改善和支链氨基酸代谢的改变有关，在tspan7修饰的小鼠中，支链α-酮酸脱氢酶复合物亚基B的表达增加就证明了这一点。机制上，TSPAN7缺乏促进皮下脂肪扩张，减轻内脏脂肪代谢应激，这是胰岛素抵抗的主要原因。结论：TSPAN7通过调节脂肪组织重塑来影响脂质代谢，特别是在高脂肪饮食暴露和衰老等代谢挑战下。其调节增强皮下脂肪储存能力，同时减轻内脏脂肪堆积，从而改善胰岛素敏感性。这些发现将TSPAN7定位为旨在改善代谢健康和预防肥胖相关疾病的治疗干预的潜在靶点。

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来源期刊

Molecular Metabolism ENDOCRINOLOGY & METABOLISM-

CiteScore

14.50

自引率

2.50%

发文量

219

审稿时长

43 days

期刊介绍： Molecular Metabolism is a leading journal dedicated to sharing groundbreaking discoveries in the field of energy homeostasis and the underlying factors of metabolic disorders. These disorders include obesity, diabetes, cardiovascular disease, and cancer. Our journal focuses on publishing research driven by hypotheses and conducted to the highest standards, aiming to provide a mechanistic understanding of energy homeostasis-related behavior, physiology, and dysfunction. We promote interdisciplinary science, covering a broad range of approaches from molecules to humans throughout the lifespan. Our goal is to contribute to transformative research in metabolism, which has the potential to revolutionize the field. By enabling progress in the prognosis, prevention, and ultimately the cure of metabolic disorders and their long-term complications, our journal seeks to better the future of health and well-being.