Exercise differentially affects metabolic functions and white adipose tissue in female letrozole- and dihydrotestosterone-induced mouse models of polycystic ovary syndrome.
Here we hypothesized that exercise in dihydrotestosterone (DHT) or letrozole (LET)-induced polycystic ovary syndrome mouse models improves impaired insulin and glucose metabolism, adipose tissue morphology, and expression of genes related to adipogenesis, lipid metabolism, Notch pathway and browning in inguinal and mesenteric fat. DHT-exposed mice had increased body weight, increased number of large mesenteric adipocytes. LET-exposed mice displayed increased body weight and fat mass, decreased insulin sensitivity, increased frequency of small adipocytes and increased expression of genes related to lipolysis in mesenteric fat. In both models, exercise decreased fat mass and inguinal and mesenteric adipose tissue expression of Notch pathway genes, and restored altered mesenteric adipocytes morphology. In conclusion, exercise restored mesenteric adipocytes morphology in DHT- and LET-exposed mice, and insulin sensitivity and mesenteric expression of lipolysis-related genes in LET-exposed mice. Benefits could be explained by downregulation of Notch, and modulation of browning and lipolysis pathways in the adipose tissue.
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden; Disciplina de Ginecologia, Laboratório de Ginecologia Estrutural e Molecular (LIM 58), Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
Rodrigo R
RR
Marcondes
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden; Endocrinology and Metabolism Laboratory, Department of Medicine, West Division, University of Chile, Santiago, Chile.
Manuel
M
Maliqueo
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Romina
R
Fornes
Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; School of Health and Education, University of Skövde, Skövde, Sweden.
Anna
A
Benrick
Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Min
M
Hu
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Niklas
N
Ivarsson
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Mattias
M
Carlström
Experimental Diabetes, Metabolism, and Nutrition Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, USA.
Samuel W
SW
Cushman
Department of Experimental Medical Sciences, Lund University, Lund, Sweden.
Karin G
KG
Stenkula
Disciplina de Ginecologia, Laboratório de Ginecologia Estrutural e Molecular (LIM 58), Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
Gustavo A R
GAR
Maciel
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden. Electronic address: elisabet.stener-victorin@ki.se.
Elisabet
E
Stener-Victorin
D017667:Adipocytes / Q000473:pathology; D050156:Adipogenesis / Q000235:genetics; D052436:Adipose Tissue, White / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001823:Body Composition; D001835:Body Weight; D048429:Cell Size; D013196:Dihydrotestosterone; D004195:Disease Models, Animal; D005247:Feeding Behavior; D005260:Female; D005786:Gene Expression Regulation; D005951:Glucose Tolerance Test; D007333:Insulin Resistance; D000077289:Letrozole; D050356:Lipid Metabolism / Q000235:genetics; D008099:Liver / Q000378:metabolism; D008810:Mice, Inbred C57BL; D009570:Nitriles; D009929:Organ Size; D010641:Phenotype; D010805:Physical Conditioning, Animal; D011085:Polycystic Ovary Syndrome / Q000235:genetics / Q000473:pathology; D015398:Signal Transduction / Q000235:genetics; D014230:Triazoles; D014280:Triglycerides / Q000378:metabolism
D009570:Nitriles; D014230:Triazoles; D014280:Triglycerides; D013196:Dihydrotestosterone; D000077289:Letrozole
Adipose tissue; Exercise; Polycystic ovary syndrome