Tohoku University clarifies how adiponectin regulates blood sugar

A research group including Lecturer Yoshiko M. Ikushima of the SiRIUS Institute of Medical Research at Tohoku University, in collaboration with the University of Edinburgh (UK), clarified that the function of adiponectin, a hormone secreted by fat cells, differs depending on dietary conditions and sex. They discovered that adiponectin is involved in regulating blood glucose and blood lipids during caloric restriction, and that adiponectin deficiency affects lipid metabolism differently in female and male mice. These findings may prove useful for personalized nutritional therapies. The study was published in PLOS Biology on June 18.

Adiponectin, which is secreted by adipose tissue, is known as a hormone that maintains low blood glucose levels. Although its blood concentration decreases in obesity and increases in lean states or during caloric restriction, its function under caloric restriction had not been fully understood.

Therefore, the research group conducted metabolic analyses, including body weight, body composition, blood glucose, blood lipids, energy expenditure, and gene expression analysis in white adipose tissue and the liver, using adiponectin global knockout (KO) mice under a normal diet and 30% caloric restriction. Because metabolic responses exhibit sex differences, both female and male mice were used.

As a result, even by adiponectin KO, there were no major differences in changes in body weight, body fat mass, muscle mass, or energy expenditure induced by caloric restriction. Surprisingly, although adiponectin is known to lower blood glucose levels, adiponectin-KO mice under caloric restriction exhibited lower blood glucose levels both during fasting and after glucose administration.

Regarding lipid metabolism, a stronger increase in blood free fatty acids was also observed during caloric restriction. Furthermore, in male adiponectin-KO mice, the ability to clear blood triglycerides (TG) was reduced under both a normal diet and caloric restriction, whereas no such effect was observed in females, indicating a sex difference.

Analysis of liver gene expression revealed that the presence or absence of adiponectin mainly affected genes involved in lipid metabolism under a normal diet and genes involved in amino acid breakdown under caloric restriction.

These findings suggest that the actions of adiponectin during caloric restriction differ from those known in obesity or under normal diet conditions, pointing to its potential involvement in regulating glucose, lipid, and amino acid metabolism during caloric restriction.

Ikushima commented, "Because adiponectin is a molecule that acts on various organs and tissues throughout the body, interpreting the data was challenging. I am pleased that we were able to report an unexpected aspect of adiponectin, which is a representative bioactive factor (adipokine) secreted by fat cells, showing that its function varies depending on dietary conditions and sex. I hope these findings contribute to a deeper understanding of dietary interventions such as caloric restriction."

Journal Information
Publication: PLOS Biology
Title: Adiponectin exerts sex-dependent effects on lipid, amino acid, and glucose metabolism during caloric restriction
DOI: 10.1371/journal.pbio.3003821