Obesity-induced diet leads to weight gain, systemic metabolic alterations, adipose tissue inflammation, hepatic steatosis, and oxidative stress in gerbils (Meriones unguiculatus)

Abstract

Background: Nowadays, the number of obese people in the world has reached alarming proportions. During the expansion of adipose tissue, a number of functions such as activation and release of cytokines and hormones may be affected. This leads the body to a pro-inflammatory pattern, which may affect the proper functioning of many tissues. Thus, studying the mechanisms by which obesity induces physiological disorders is necessary, and may be facilitated by the use of animal models, in particular rodents. We sought to characterize the metabolic and adipose tissue changes resulting from a diet rich in fats and simple sugars in gerbils.

Methods: We divided 14 gerbils into two experimental groups that received a diet rich in simple carbohydrates and fats with 5,86 kcal/g (OB, n = 7) or a standard diet with 4.15 kcal/g (CT; n = 7) for 11 weeks. The animals had free access to water and food. The animal weight and food consumption were measured weekly. Blood, adipose tissue and liver of each animal were collected at the end of experiment. The following parameters were determined: cholesterol (COL), triglycerides (TGL) and glycemia (GLI) in the plasma; cytokines (IL-6, IL-10 and TNF-α) and hormones (adiponectin and leptin) in adipose tissue; activity of superoxide dismutase (SOD) and catalase (CAT), extraction and differentiation of fat and histology in liver.

Results: The consumption of a diet rich in simple carbohydrates and fats led to increased total body weight and increased relative weights of liver and adipose tissue. In addition, we observed increased fasting glucose levels and circulating triglycerides, along with high TNF-α production in adipose tissue and increased total fat, cholesterol and triglyceride contents in the liver, contributing to higher intensity of hepatic steatosis. On the other hand, the animals of this group showed depletion in the enzyme activity of SOD and CAT in the liver, as well as reduction of IL-10 and adiponectin levels in adipose tissue.

Discussion: High intake of saturated fat and simple carbohydrates establish the gerbil as an experimental model for the study of metabolic and hepatic abnormalities resulting from obesity.

Keywords: Animal models; Diet-induced obesity; Lipid metabolism; Obesity.

Figure 1. (A) Total body weight, ratio of (B) Liver (% body weight) and (C) Epididymal fat (% body weight), and (D) Total caloric intake (Kcal/week) in gerbil fed control (CT) or hyper (OB) diets during 11 weeks.

Data were represented as means ± S.E.M. n = 7 per group. Statistical significance was indicated as (***) for p < 0.001 or (****) for p < 0.0001. T-test used for all data.

Figure 2. Fatty acid intake in gerbil fed control (CT) or hyper (OB) diets during 11 weeks.

Data were represented as means ± S.E.M. n = 7 per group. Statistical significance was indicated as (****) for p < 0.0001. T-test used for all data. SFA, saturated fatty acid, MUFA, monounsaturated fatty acid, PUFA, polyunsaturated fatty acid.

Figure 3. Photomicrograph of the liver tissue CT and OB groups (A) Control group showing normal liver parenchyma. (B) Obese group showing microvesicular (arrowheads) steatosis, but mainly the presence of large negative cytoplasmic vacuoles (arrow) that pushes the nucleus to the periphery of the hepatocyte, increases its size and compress the sinusoid capillaries.

Bar = 100 µm.

Figure 4. Morphometric analysis of steatosis area in liver tissue of Control and Obese gerbils after 11 weeks of Hyper diet.

Data were represented as means ± S.E.M. n = 7 per group. Statistical significance was indicated as (***) for p < 0.001 by Mann–Whitney test.

Figure 5. Adipose tissue concentration of the adipokines (A) IL-6, (B) IL-10, (C) TNF-α, (D) Adiponectin and (E) Leptin.

Data were represented as means ± S.E.M. n = 7 per group. Statistical significance was indicated as (***) for p < 0.001 or (****) for p < 0.0001. Mann–Whitney test used in IL-6, IL-10 and Adiponectin. T-test used in TNF-α and Leptin.