Intra-Abdominal Fat Adipocyte Hypertrophy through a Progressive Alteration of Lipolysis and Lipogenesis in Metabolic Syndrome Rats

Abstract

This study evaluates the progressive participation of enzymes involved in lipolysis and lipogenesis, leading to adipocyte hypertrophy in a metabolic syndrome (MS) rat model caused by chronic consumption of 30% sucrose in drinking water. A total of 70 male Wistar rats were divided into two groups: C and MS. Each of these groups were then subdivided into five groups which were sacrificed as paired groups every month from the beginning of the treatment until 5 months. The intra-abdominal fat was dissected, and the adipocytes were extracted. Lipoprotein lipase (LPL), hormone-sensitive lipase (HSL), protein kinases A (PKA), and perilipin A expressions were determined. The LPL and HSL activities were evaluated by spectrophotometry. Histological staining was performed in adipose tissue. Significant increases were observed in blood pressure, HOMA-IR, leptin, triglycerides, insulin, intra-abdominal fat, and number of fat cells per field (p = 0.001) and in advanced glycosylation products, adipocyte area, LPL, HSL activities and/or expression (p ≤ 0.01) in the MS groups progressively from the third month onward. Lipogenesis and lipolysis were increased by LPL activity and HSL activity and/or expression. This was associated with hyperinsulinemia and release of non-esterified fatty acids causing a positive feedback loop that contributes to the development of adipocyte hypertrophy.

Keywords: adipocyte; hormone-sensitive lipase; hypertrophy; lipoprotein lipase; metabolic syndrome; perilipin A.

Figure 1

Representative histograms: (A) intra-abdominal fat. (B) Fat cell number per gram of tissue. (C) Adipocyte cell number for field and (D) adipocyte diameter. Data show the mean ± SEM; n = 7 rats per experimental group. Abbreviations: C = Control; MS = Metabolic syndrome; M = Month.

Figure 2

Representative photomicrographs of intra-abdominal white tissue from the experimental groups that show adipocyte size. Five fields per sample were analyzed. Panels (A) 1 M, (B) 2 M, (C) 3 M, (D) 4 M and (E) 5 M represent the C, and panels (F) 1 M, (G) 2 M, (H) 3 M, (I) 4 M and (J) 5 M represent the MS groups. n = 7 rats per experimental group. Abbreviations: C = Control; MS = Metabolic syndrome; M = Month.

Figure 3

Effect of 30% chronic sucrose on the LPL (A) and HSL (B) activities through the five months of the treatment determined in the adipocyte homogenates in the experimental groups. Values are the mean ± SEM, n = 7 rats per experimental group. Abbreviations: C = Control; MS = Metabolic syndrome; LPL = Lipoprotein lipase; M = Month; HSL = Hormone sensitive lipase.

Figure 4

Representative histograms of the PKA/GAPDH expression (A) and Perilipin A/GAPDH expression (B). Values are the mean ± SEM n = 7 rats per experimental group. Abbreviations: C = Control; MS = Metabolic syndrome; PKA = Protein kinase A; GAPDH = Glyceraldehyde-3-phosphate dehydrogenase; M = Month.

Figure 5

Representative histograms of HSL/GAPDH expression (A) and LPL/GAPDH expression (B). Values are the mean ± SEM, n = 7 rats per experimental group. Abbreviations: C = Control; MS = Metabolic syndrome; LPL = Lipoprotein lipase; M = Month; HSL = Hormone sensitive lipase.