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The central nervous system (CNS) orchestrates the whole-body metabolism. Within the CNS, the hypothalamus plays a dominant role in the regulation of metabolic homeostasis in response to dynamic challenges such as hypoglycemia, cold-exposure, and exercise. Our previous work articulates that neurons in the dorsomedial and central parts of ventromedial hypothalamic nucleus (VMHdm/c neurons) substantially contribute to metabolic adaptations to exercise training including augmented skeletal muscle mass and basal metabolic rate in mice. Knockdown of steroidogenic factor-1 (SF-1) in VMHdm/c neurons hampers exercise-induced mRNA expression of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (Pgc-1α) in skeletal muscle. PGC-1α is a key transcriptional regulator that controls a broad range of genes related to glucose and fat metabolism, mitochondrial functionangiogenesis, and protein synthesis. Loss- or gain-of-function of PGC-1α in skeletal muscle dramatically changes skeletal muscle physiology as well as whole-body metabolism. These data suggest that VMHdm/c neurons expressing SF-1 (VMHdm/cSF-1 neurons) mediate metabolic responses of skeletal muscle to exercise, thereby contributing to metabolic benefits of exercise. However, the mechanisms by which VMHdm/cSF-1 neurons mediate exercise-induced augmented skeletal muscle PGC-1α expression remains unclear. In particular, the pathway from VMHdm/cSF-1 neurons to skeletal muscle has yet to be unraveled.

 

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Sema7A protects against high-fat diet-induced obesity and hepatic steatosis by regulating adipo/lipogenesis

Qiongyu Lu, Ziting Liu, Luyao Zhao, Linru Xu, ... Li Zhu

Sema7A protects against high-fat diet-induced obesity and hepatic steatosis by regulating adipo/lipogenesis

Objective

Obesity and related diseases are becoming a growing risk for public health around the world due to the westernized lifestyle. Sema7A, an axonal guidance molecule, has been known to play a role in neurite growth, bone formation, and immune regulation. Whether Sema7A participates in obesity and metabolic diseases is unknown. As several SNPs in SEMA7A and its receptors were found to correlate with BMI and metabolic parameters in the human population, we investigated the potential role of Sema7A in obesity and hepatic steatosis.

Methods

GWAS and GEPIA database was used to analyze SNPs in SEMA7A and the correlation of Sema7A expression with lipid metabolism related genes. Sema7A−/− mice and recombinant Sema7A (rSema7A) were used to study the role of Sema7A in HFD-induced obesity and hepatic steatosis. Adipose tissue-derived mesenchymal stem cells (ADSCs) were used to examine the role of Sema7A in adipogenesislipogenesis and downstream signaling.

Results

Deletion of Sema7A aggravated HFD-induced obesity. Sema7A deletion enhanced adipogenesis in both subcutaneous and visceral ADSCs, while the addition of rSema7A inhibited adipogenesis of ADSCs and lipogenesis of differentiated mature adipocytes. Sema7A inhibits adipo/lipogenesis potentially through its receptor integrin β1 and downstream FAK signaling. Importantly, administration of rSema7A had protective effects against diet-induced obesity in mice. In addition, deletion of Sema7A led to increased hepatic steatosis and insulin resistance in mice.

Conclusions

Our findings reveal a novel inhibitory role of Sema7A in obesity and hepatic steatosis, providing a potential new therapeutic target for obesity and metabolic diseases.

Sema7A protects against high-fat diet-induced obesity and hepatic steatosis by regulating adipo/lipogenesis

Qiongyu Lu, Ziting Liu, Luyao Zhao, Linru Xu, ... Li Zhu

Sema7A protects against high-fat diet-induced obesity and hepatic steatosis by regulating adipo/lipogenesis

Objective

Obesity and related diseases are becoming a growing risk for public health around the world due to the westernized lifestyle. Sema7A, an axonal guidance molecule, has been known to play a role in neurite growth, bone formation, and immune regulation. Whether Sema7A participates in obesity and metabolic diseases is unknown. As several SNPs in SEMA7A and its receptors were found to correlate with BMI and metabolic parameters in the human population, we investigated the potential role of Sema7A in obesity and hepatic steatosis.

Methods

GWAS and GEPIA database was used to analyze SNPs in SEMA7A and the correlation of Sema7A expression with lipid metabolism related genes. Sema7A−/− mice and recombinant Sema7A (rSema7A) were used to study the role of Sema7A in HFD-induced obesity and hepatic steatosis. Adipose tissue-derived mesenchymal stem cells (ADSCs) were used to examine the role of Sema7A in adipogenesislipogenesis and downstream signaling.

Results

Deletion of Sema7A aggravated HFD-induced obesity. Sema7A deletion enhanced adipogenesis in both subcutaneous and visceral ADSCs, while the addition of rSema7A inhibited adipogenesis of ADSCs and lipogenesis of differentiated mature adipocytes. Sema7A inhibits adipo/lipogenesis potentially through its receptor integrin β1 and downstream FAK signaling. Importantly, administration of rSema7A had protective effects against diet-induced obesity in mice. In addition, deletion of Sema7A led to increased hepatic steatosis and insulin resistance in mice.

Conclusions

Our findings reveal a novel inhibitory role of Sema7A in obesity and hepatic steatosis, providing a potential new therapeutic target for obesity and metabolic diseases.

2021 impact factor: 8.568

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