title: Sex-dependent differences in rat hepatic lipid accumulation and insulin sensitivity in response to diet-induced obesity.
abstract: Ectopic deposition of lipids in liver and other extrahepatic tissues alters their function and occurs once adipose tissue fat storage capacity is exceeded. We investigated sexual dimorphism in the effects of dietary obesity on the liver insulin signaling pathway, as well as its connection to differences in hepatic fat accumulation. Ten-week-old Wistar rats of both sexes were fed a standard diet or a high-fat diet for 26 weeks. Insulin, adipokine levels, and glucose tolerance were measured. Lipid content, PPARα mRNA expression and protein levels of insulin receptor subunit β (IRβ), IR substrate 2 (IRS-2), Ser/Thr kinase A (Akt), and pyruvate dehydrogenase kinase isozyme 4 (PDK4) were measured in liver. In control rats, serum parameters and hepatic levels of IRβ, IRS-2, and Akt proteins pointed to a profile of better insulin sensitivity in females. In response to dietary treatment, female rats exhibited a greater increase in body mass and adiposity and lower liver fat accumulation than males, but maintained better glucose tolerance. The reduced insulin signaling capacity in the liver of obese female rats seems to prevent lipid accumulation and probably lipotoxicity-associated hepatic disorders.
authors.affiliation: Grup de Metabolisme Energètic i Nutrició, Departament de Biologia Fonamental i Ciències de la Salut, Institut Universitari d'Investigació en Ciències de la Salut (IUNICS), Universitat de les Illes Balears, Cra. Valldemossa km 7.5. E-07122 Palma de Mallorca, Spain.
authors.forename: Antònia
authors.initials: A
authors.lastname: Nadal-Casellas
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Proenza
authors.forename: Isabel
authors.initials: I
authors.lastname: Lladó
authors.forename: Magdalena
authors.initials: M
authors.lastname: Gianotti
mesh_terms: D052242:Adiponectin / Q000097:blood; D050154:Adiposity; D000818:Animals; D001786:Blood Glucose; D001835:Body Weight; D059305:Diet, High-Fat / Q000009:adverse effects; D002149:Energy Intake; D005260:Female; D014644:Genetic Variation; D007328:Insulin / Q000097:blood; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D007333:Insulin Resistance; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009765:Obesity / Q000209:etiology / Q000378:metabolism*; D009929:Organ Size; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D051381:Rats; D017208:Rats, Wistar; D011972:Receptor, Insulin / Q000378:metabolism; D012737:Sex Factors; D014280:Triglycerides / Q000097:blood
chemical_list: D052242:Adiponectin; D001786:Blood Glucose; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D047493:PPAR alpha; C000631440:Pdk4 protein, rat; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D014280:Triglycerides; D011972:Receptor, Insulin; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt