Key result
Exercise increased adiponectin levels and reduced betatrophin levels in insulin-resistant mice, modulating the LKB1/AMPK/PGC-1α signaling axis.
Why the study?
It was hypothesized that the adiponectin pathway regulates betatrophin in the liver, but whether exercise and adiponectin affect betatrophin to improve insulin resistance in mice remained unknown.
Does exercise and adiponectin administration reduce betatrophin levels in insulin-resistant mice?
Does exercise and adiponectin administration reduce betatrophin levels in insulin-resistant mice?
Exercise reverses pathogenic changes in adiponectin and betatrophin levels in insulin-resistant mice, modulating the LKB1/AMPK/PGC-1α signaling axis.
May inform adiponectin-betatrophin links in metabolic models; leaves open human relevance for T2D therapies.
Aims: Adiponectin stimulates mitochondrial biogenesis through peroxisome proliferator-activated receptor-coactivator1α (PGC-1α), a major regulator of mitochondrial biogenesis, and its effect on the genesis of insulin resistance is organ-specific. Expressed predominantly in fat and liver tissues, betatrophin is primarily involved in lipid metabolism, and could be a putative therapeutic target in metabolic syndrome and T2D. We hypothesized that the adiponectin pathway may regulate the production and/or secretion of betatrophin in liver. We aimed to determine whether exercise and adiponectin affect betatrophin to improve insulin resistance in mice. Methods: To investigate this hypothesis, we used wild-type C57BL/6 mice subjected to a high-fat diet, an exercise regimen, and i.p. injection of recombinant mouse adiponectin (Acrp30), and adiponectin knockout (Adipoq−/−) mice (C57BL/6 background) subjected to i.p. injection of Acrp30. Results: In Adipoq–/– mice, betatrophin levels in the plasma and liver were upregulated. In mice, plasma and liver betatrophin levels were significantly upregulated following a high-fat diet. Exercise and i.p. Acrp30 downregulated betatrophin levels and increased adiponectin mRNA and protein expression in the plasma and liver. The trend of change in PGC-1α and betatrophin levels in the liver was consistent. Conclusions/interpretation: Exercise reverses pathogenic changes in adiponectin and betatrophin levels in insulin-resistant mice. Exercise increased adiponectin levels and reduced betatrophin levels. Furthermore, exercise reduced betatrophin levels via adiponectin, which modulated the LKB1/AMPK/PGC-1α signaling axis but was not solely dependent on it for exerting its effects.
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Guo et al. (2022) studied Insulin resistance. Exercise and recombinant mouse adiponectin (Acrp30) was evaluated on Betatrophin and adiponectin levels. Exercise increased adiponectin levels and reduced betatrophin levels in insulin-resistant mice, modulating the LKB1/AMPK/PGC-1α signaling axis.
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