Caloric intake that exceeds caloric expenditure is the main driver of obesity. Brown fat is characterized by the abundant mitochondria and could dissipate energy as heat, thus giving a feasible way to combat obesity. With the advent of GLP-1 receptor agonist in medical practice for diabetes treatment, peptide drug has been an important element in the pharmaceutical landscape. Discovery of bioactive peptide is hence increasingly appreciated. Presently, we identified an endogenous peptide, TPDHM1, from β-casein in milk. We further demonstrated its function in activating adipose tissue thermogenesis and the potential molecular mechanism involved. Our results confirmed that TPDHM1 could promote brown and white adipocytes energy metabolism both in vitro and in vivo. Chronic administration of TPDHM1 attenuated the high-fat diet induced obesity. Additionally, the insulin resistance and hyperglycemia of diabetic db/db mice were improved following TPDHM1 treatment. Mechanistically, both RNA-seq and protein microarray results revealed that the thermogenic effect of TPDHM1 is possibly mediated by p38-mitogen-activated protein kinase (p38-MAPK) signaling pathway. Inhibition of the p38-MAPK by SB203580 abolished the UCP-1 expression induced by TPDHM1. Taken together, our data suggest that TPDHM1 can potentially alleviate obesity and diabetes by stimulating energy metabolism via p38-MAPK pathways.


H. Zhong: None. X. Zhang: None. Z. Zhang: None. X. Chi: None. C. Ji: None. X. Cui: None.


National Natural Science Foundation of China (81770837, 81770866, 81900783)

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