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| 2024-01-16 08:42:25 | onclick： | New Study Offers New Strategies for Reducing Obesity |
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Journal of the National Academy of Sciences in the United States published the original research results of Zhang Huijie, the chief physician of the endocrine metabolism department of Southern Medical University Southern Hospital.The research results provide new ideas and strategies for alleviating obesity's high-calorie state and improving metabolic state.
The essence of obesity is the imbalance between energy intake and consumption.Brown adipose tissue, which produces heat because it contains a large number of mitochondria, is the main site of adaptive heat production and plays a key role in energy balance and fuel metabolism in mammals.However, the mechanism of heat production regulation in brown adipose tissue is still unclear, and many factors regulating brown adipose tissue activity have been neglected and have not been fully explored.
Interleukin 6 (IL-6) cytokine family is a group of proteins that play a key role in various physiological processes. Previous studies have shown that some members of the family are involved in weight loss and energy consumption.
To identify members of the IL-6 family who can regulate heat production in brown adipose tissue, the researchers first conducted transcriptomics analysis of brown adipose tissue in acute cold-stimulated C57BL/6 mice.CLCF1 can promote recruitment of gp130 and leukemia suppressor receptors by binding to ciliary neurotrophic factor receptors during tumorigenesis and phosphorylation of CLCF1 gene mutations can also lead to cold-induced sweating syndrome.However, the role of CLCF1 in energy homeostasis remains unclear.
It was found that CLCF1 expression decreased significantly when heat production was activated, while obesity induced CLCF1 expression upregulated in brown adipose tissue.In order to investigate the effect and mechanism of CLCF1 on heat production in brown adipose tissue, the researchers first injected the adenovirus into brown adipose tissue in situ.Next, the researchers further constructed brown adipocyte-specific knockout mice (Clcf1BTKO), which found higher body temperature and metabolic rates, and brown adipose tissue with more multicellular adipocytes and mitochondria than control mice.
In addition, CLCF1 knock-out in brown adipose tissue significantly increased energy consumption, reduced weight gain, and improved impaired glucose and lipid metabolic homeostasis in mice.Adenylate cyclase 3 (ADCY3) is the downstream target gene of CLCF1 by transcriptome analysis of brown adipose tissue of Clcf1BTKO mice. Furthermore, combined with acute cold stimulation brown adipose tissue transcriptome analysis, CLCF1 knock-out significantly activates PERK-ATF4 signaling.CLCF1 inhibits the transcriptional activity of ADCY3 by inhibiting PERK-ATF4 signaling axis, and then inhibits PKA substrate phosphorylation, thus impairing the thermal production of brown adipose tissue.
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