Cell Biochem Funct. 2013 Aug;31(6):504-10. doi: 10.1002/cbf.2927.

High-fat diet feeding induces sex-dependent changes in inflammatory and insulin sensitivity profiles of rat adipose tissue.

Maria E. Estrany1,2, Ana M. Proenza1,2, Magdalena Gianotti1,2 and Isabel Lladó1,2

1 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, Palma de Mallorca, Spain

2 Ciber Fisiopatología Obesidad y Nutrición (CB06/03), Instituto de Salud Carlos III, Madrid, Spain



The aim of the study was to determine, in rats of both sexes, the effect of HF diet feeding on the expression of adipokines involved in inflammatory status and insulin sensitivity and on the levels of proteins involved in lipid handling of retroperitoneal adipose tissue. Eight-week-old Wistar rats of both sexes were fed a control diet (2.9% w/w fat) or an HF diet (30% w/w fat) for 14 weeks. Adiponectin, peroxisome proliferator–activated receptor g and inflammatory marker mRNA levels were analyzed by real-time polymerase chain reaction. Levels of insulin receptor, glucose transporter 4, carnitine palmitoyl transferase 1, fatty acid synthase, hormone-sensitive lipase and lipoprotein lipase were determined by Western blot. HF diet feeding did not induce hyperphagia or body weight gain but did promote an increase in adiposity although only in male rats. HF diet impaired glucose tolerance and the expression of inflammatory and insulin sensitivity markers in adipose tissue of male rats, but not in female rats. Male rats seem to be more prone to disorders associated with an unbalanced composition of the diet, even in the absence of hyperphagia. In contrast, female rats counteract excessive fat intake by improving their ability to use lipid fuels, which limits adiposity and maintains insulin sensitivity.

Copyright © 2012 John Wiley & Sons, Ltd.

KEYWORDS: adiponectin, adiposity, high-fat diet, insulin sensitivity, sexual dimorphism

PMID: 23112138



Evidence shows that the consumption of unbalanced high-fat (HF) diets increases body weight and fat accumulation, particularly in visceral adipose tissue, which is most associated with the increased health risks of obesity. Traditionally, adipose tissue has been considered the primary site for whole body energy storage, however currently the adipose tissue is considered an endocrine organ extraordinarily active that produces a large variety of proteins called adipokines. Many adipokines are linked to insulin sensitivity and/or are related to the chronic inflammatory status that accompanies obesity. In fact, the endocrine profile of the adipose tissue is altered in the obese status. Inflammation plays an important role in the initiation and development of some obesity-related disorders, such as type 2 diabetes, cardiovascular diseases and other components of metabolic syndrome, such as insulin resistance. Females have been found to display less serious obesity-related conditions (e.g. insulin resistance) than males in a variety of studies conducted in both humans and animals.

Usually, HF diets that provoke serious metabolic disorders induce hyperphagia and significant body weight gains. The obesity model used in the present study induces a greater adiposity and insulin resistance profile in male rats compared to females, without hyperphagia neither body weight gain. In order to deepen in this sexual dimorphism and elucidate the main factors involved we determine the sex-dependent changes in the adipose tissue expression of inflammatory adipokines and markers of insulin sensitivity and lipid handling.

The results highlight important differences between sexes in adipose tissue inflammatory status in response to HF diet feeding (Figure 1). Thus, male rats show greater body fat deposition and macrophage infiltration than females, which provokes an impairment of adipose tissue endocrine function. This has resulted in a more marked inflammatory profile and impaired insulin sensitivity in male rats. Female rats get limit body fat accumulation and maintain insulin sensitivity improving the handling of lipid fuels and, therefore, counteracting excessive fat intake.


In summary, we suggest that male rats could have increased risk of suffering metabolic syndrome-related disorders in comparison with females in response to the same unbalanced diet.

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