Abstract
This dataset contains data for a manuscript that is being submitted for publication in September 2024. Once published, this dataset will be updated with the DOI for the manuscript. The Abstract for the current version of the manuscript is as follows:
Adiponectin is the most-abundant hormone in the circulation. Despite being secreted almost exclusively by adipocytes, circulating adiponectin decreases in obesity and insulin resistance but increases in lean states, including caloric restriction (CR) in animals and humans. Preclinical studies suggest that, in obesity and other adverse contexts, adiponectin deficiency promotes cardiometabolic dysfunction whereas increasing adiponectin improves cardiometabolic health. However, the fundamental roles of adiponectin in physiological, evolutionarily relevant contexts, including hyperadiponectinaemia during CR, have been largely overlooked. We hypothesised that increased adiponectin contributes to the metabolic benefits of CR, including greater glucose tolerance and fat oxidation. To test this, we investigated the effect of global adiponectin knockout (KO) in male and female mice fed ad libitum (AL) or 30% CR from 9-13 weeks of age. Adiponectin KO did not alter CR’s effects on body mass or composition but, unexpectedly, enhanced CR’s ability to improve glucose tolerance. This occurred without altering insulin sensitivity or secretion and instead was driven by fasting hypoglycaemia in KO mice during CR. Adiponectin KO also augmented CR-induced increases in plasma fatty acids but did not alter systemic lipid oxidation in either sex. Hepatic triglycerides and sphingolipids were also unaffected by adiponectin deficiency; however, RNAseq revealed that, during CR, KO compromised hepatic gluconeogenesis in males and promoted hepatic amino acid catabolism in both sexes. This occurred without sarcopenia or elevated protein catabolism in skeletal muscle. Instead, RNAseq indicated that adiponectin KO impaired mitochondrial metabolism and stimulated immunological activity in skeletal muscle of CR males, while CR females’ muscle was largely unaffected. Our study is the first to investigate the role of adiponectin in CR’s metabolic effects. Together, our findings suggest that, in both sexes, adiponectin evolved to help maintain blood glucose during prolonged fasting and that variation in adiponectin influences CR’s metabolic benefits. We contend that the widely reported functions of adiponectin in pathological contexts, such as obesity and insulin resistance, differ substantially to its roles during CR and other physiological conditions in which circulating adiponectin is increased.
For further details please see the file named "Readme metadata file"
Adiponectin is the most-abundant hormone in the circulation. Despite being secreted almost exclusively by adipocytes, circulating adiponectin decreases in obesity and insulin resistance but increases in lean states, including caloric restriction (CR) in animals and humans. Preclinical studies suggest that, in obesity and other adverse contexts, adiponectin deficiency promotes cardiometabolic dysfunction whereas increasing adiponectin improves cardiometabolic health. However, the fundamental roles of adiponectin in physiological, evolutionarily relevant contexts, including hyperadiponectinaemia during CR, have been largely overlooked. We hypothesised that increased adiponectin contributes to the metabolic benefits of CR, including greater glucose tolerance and fat oxidation. To test this, we investigated the effect of global adiponectin knockout (KO) in male and female mice fed ad libitum (AL) or 30% CR from 9-13 weeks of age. Adiponectin KO did not alter CR’s effects on body mass or composition but, unexpectedly, enhanced CR’s ability to improve glucose tolerance. This occurred without altering insulin sensitivity or secretion and instead was driven by fasting hypoglycaemia in KO mice during CR. Adiponectin KO also augmented CR-induced increases in plasma fatty acids but did not alter systemic lipid oxidation in either sex. Hepatic triglycerides and sphingolipids were also unaffected by adiponectin deficiency; however, RNAseq revealed that, during CR, KO compromised hepatic gluconeogenesis in males and promoted hepatic amino acid catabolism in both sexes. This occurred without sarcopenia or elevated protein catabolism in skeletal muscle. Instead, RNAseq indicated that adiponectin KO impaired mitochondrial metabolism and stimulated immunological activity in skeletal muscle of CR males, while CR females’ muscle was largely unaffected. Our study is the first to investigate the role of adiponectin in CR’s metabolic effects. Together, our findings suggest that, in both sexes, adiponectin evolved to help maintain blood glucose during prolonged fasting and that variation in adiponectin influences CR’s metabolic benefits. We contend that the widely reported functions of adiponectin in pathological contexts, such as obesity and insulin resistance, differ substantially to its roles during CR and other physiological conditions in which circulating adiponectin is increased.
For further details please see the file named "Readme metadata file"
| Date made available | 19 Sept 2024 |
|---|---|
| Publisher | Edinburgh DataShare |