This Article Full Text Full Text (PDF) All Versions of this Article: 148/10/4658    most recent Author Manuscript (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Nonogaki, K. Articles by Oka, Y. Search for Related Content PubMed PubMed Citation Articles by Nonogaki, K. Articles by Oka, Y. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Substance via MeSH Medline Plus Health Information Diabetes Nutrition Obesity

Social Isolation Affects the Development of Obesity and Type 2 Diabetes in Mice

Center of Excellence, Division of Molecular Metabolism and Diabetes, Tohoku University Graduate School of Medicine, Miyagi 980-8575, Japan

Address all correspondence and requests for reprints to: Katsunori Nonogaki, M.D., Ph.D., Associate Professor, Center of Excellence, Division of Molecular Metabolism and Diabetes, Tohoku University Graduate School of Medicine, 2-1 Seiryou-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan. E-mail: knonogaki-tky{at}umin.ac.jp.

Social isolation is associated with increased risks of mortality and morbidity. In this study, we show that chronic individual housing accelerated body weight gain and adiposity in KK mice but not C57BL6J mice, and fully developed diabetes in KKA^y mice. Individually housed KK and KKA^y mice increased body weight gain over the initial 2 wk without increased daily average food consumption compared with group-housed animals. The individually housed KK and KKA^y mice then gradually increased food consumption for the next 1 wk. The chronic social isolation-induced obesity (SIO) was associated with hyperleptinemia and lower plasma corticosterone and active ghrelin levels but not hyperinsulinemia. Elevated plasma leptin in the SIO suppressed expression of 5-HT2C receptor in white adipose tissue. The SIO was also associated with decreased expression of ß3-adrenergic receptors in white adipose tissue and hypothalamic leptin receptor, which might be secondary to the enhanced adiposity. Interestingly, social isolation acutely reduced food consumption and body weight gain compared with group-housed obese db/db mice with leptin receptor deficiency. Social isolation-induced hyperglycemia in KKA^y mice was associated with increased expression of hepatic gluconeogenetic genes independent of insulin. These findings suggest that social isolation promotes obesity due to primary decreased energy expenditure and secondary increased food consumption, which are independent of the disturbed leptin signaling, in KK mice, and develops into insulin-independent diabetes associated with increased expression of hepatic gluconeogenetic genes in KKA^y mice. Thus, social isolation can be included in the environmental factors that contribute to the development of obesity and type 2 diabetes.