Cited by 115Regulation of Appetite and ObesityAdipokines, Inflammation, and Metabolic DiseasesAdipose Tissue and Metabolism

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

Nonogaki, Katsunori, Nozue, Kana, Oka, Yoshitomo·2007·Endocrinology

DOI 10.1210/en.2007-0296

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Abstract

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 KKAy mice. Individually housed KK and KKAy 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 KKAy 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 β3-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 KKAy 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 KKAy mice. Thus, social isolation can be included in the environmental factors that contribute to the development of obesity and type 2 diabetes.

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Authors: Nonogaki, K., Nozue, K., & Oka, Y.
Affiliations: Tohoku University (JP)
ORCID: Nonogaki, Katsunori
Venue: Endocrinology
Publisher: The Endocrine Society
Published: 2007-10-01
Volume: 148
Issue: 10
Pages: 4658-4666
ISSN: 0013-7227 (ISSN-L)
1945-7170
DOI: 10.1210/en.2007-0296
OpenAlex: W2032850135
Cited by: 115
References: 34
Citations by year: 2025: 8 · 2024: 6 · 2023: 11 · 2022: 14 · 2021: 8 · 2020: 10 · 2019: 2 · 2018: 9 · 2017: 10 · 2016: 4 · 2015: 5 · 2014: 5 · 2013: 5 · 2012: 1
FWCI: 1.75
Type: journal article
Language: en
Open access: closed
Locations: Endocrinology (publishedVersion)
PubMed (publishedVersion)
Funders: U.S. Public Health Service (KH 21016)
Topics: Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
Keywords: social isolation, obesity, type 2 diabetes, KK mice, leptin, hyperleptinemia, 5-HT2C receptor, beta3-adrenergic receptor, leptin receptor, dietary intake, energy expenditure, hepatic gluconeogenesis, corticosterone, ghrelin, white adipose tissue
MeSH terms: Uncoupling Protein 2, Uncoupling Protein 1, Adipose Tissue, Animals, Body Weight, Diabetes Mellitus, Type 2, Eating, Energy Metabolism, Homeostasis, Ion Channels, Male, Mice, Inbred C57BL, Mice, Mutant Strains, Obesity, Organ Size, RNA, Messenger, Social Isolation, Gene Expression, Disease Progression, Muscle, Skeletal, Leptin, Mitochondrial Proteins, Receptor, Serotonin, 5-HT2C, Peroxisome Proliferator-Activated Receptors, Mice

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

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