Serotonin transporter deficiency increases abdominal fat in female, but not male rats.
Depression and abdominal obesity often co-occur, predominantly in women, and are associated with an increased risk for the development of glucose intolerance and subsequently type 2 diabetes. The underlying mechanisms are poorly understood. We found that female, but not male, depression-prone serotonin transporter knockout (SERT(-/-)) rats had a strong increase (54%) in abdominal fat, whereas no increases in plasma concentrations of glucose and insulin were observed. Surprisingly, application of a high-fat, high-sucrose (HFHS)-choice diet, which results in increased abdominal fat deposition and increased plasma glucose levels in wild-type rats, did not result in elevated plasma glucose levels in female SERT(-/-) rats. Our results show that serotonin transporter deficiency affects abdominal fat deposition in a sex-dependent way, but protects against rises in glucose levels, and thereby potentially glucose intolerance. The increased abdominal fat formation could result from serotonin-mediated developmental changes and provides heuristic value for understanding the effects of the depression-associated serotonin transporter promoter polymorphism in humans.
Homberg
Judith R
JR
Functional Genomics and Bioinformatics, Hubrecht Institute, University Medical Center Utrecht, Utrecht, The Netherlands.
la Fleur
Susanne E
SE
Cuppen
Edwin
E
D050153:Abdominal Fat / Q000378:metabolism*; D052242:Adiponectin / Q000097:blood; D052436:Adipose Tissue, White / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D001786:Blood Glucose / Q000235:genetics / Q000378:metabolism; D001835:Body Weight / Q000235:genetics*; D004032:Diet; D004040:Dietary Carbohydrates; D004041:Dietary Fats; D004435:Eating / Q000235:genetics; D005260:Female; D007328:Insulin / Q000097:blood / Q000235:genetics; D020738:Leptin / Q000097:blood; D008297:Male; D051381:Rats; D055647:Rats, Transgenic; D017208:Rats, Wistar; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D012727:Sex Characteristics
D052242:Adiponectin; D001786:Blood Glucose; D004040:Dietary Carbohydrates; D004041:Dietary Fats; D007328:Insulin; D020738:Leptin; D050486:Serotonin Plasma Membrane Transport Proteins