Therapeutic effects of globular adiponectin in diabetic rats with nonalcoholic fatty liver disease

Abstract

Aim: To explore the therapeutic role of globular adiponectin (gAd) in high-fat diet/streptozotocin (STZ)-induced type 2 diabetic rats with nonalcoholic fatty liver disease (NAFLD).

Methods: Seven rats were fed a basic diet (normal control group; NC) during the experiment. Experimental rats (14 rats) were given a high-fat diet for 4 wk and were then injected with STZ to induce type 2 diabetes mellitus (T2DM) and NAFLD. Half of the T2DM/NAFLD rats were randomly injected intraperitoneally with gAd for 7 d (gAd-treated group), while the other 7 rats (T2DM/NAFLD group) received 0.9% saline. Plasma biochemical parameters and insulin concentrations were measured. Liver histopathology was examined by hematoxylin-eosin staining. Insulin receptor expression in the liver was analyzed by immunohistochemical staining, Western blot and quantitative real-time reverse transcription polymerase chain reaction analysis.

Results: Compared to the control group, the T2DM/NAFLD group had increased levels of glucolipid and decreased levels of insulin. Plasma glucose and lipid levels were decreased in the gAd-treated group, while serum insulin levels increased. The expression of insulin receptor in the T2DM/NAFLD group increased compared with the NC group, and gAd downregulated insulin receptor expression in the livers of T2DM/NAFLD rats. Steatosis of the liver was alleviated in the gAd-treated group compared to the T2DM/NAFLD group (NAS 1.39 ± 0.51 vs 1.92 ± 0.51, P < 0.05).

Conclusion: Globular adiponectin exerts beneficial effects in T2DM rats with NAFLD by promoting insulin secretion, mediating glucolipid metabolism, regulating insulin receptor expression and alleviating hepatic steatosis.

Keywords: Adiponectin; Insulin receptor; Insulin secretion; Steatosis.

Figure 1

Changes in hepatic histology. A: Normal control group; B: Type 2 diabetes mellitus/nonalcoholic fatty liver disease group; C: Globular adiponectin-treated group (hematoxylin-eosin staining, × 200).

Figure 2

Immunohistochemical staining for insulin receptor in liver tissues. A: Normal control (NC) group; B: Type 2 diabetes mellitus/nonalcoholic fatty liver disease (T2DM/NAFLD) group; C: Globular adiponectin (gAd)-treated group (× 400); D: Bar graph represents the relative expression levels of insulin receptor (IR) in the NC, T2DM/NAFLD and gAd-treated groups based on the intensity and extent of staining. The values are depicted as mean ± SD (n = 7). T2DM/NAFLD vs gAd-treated, ^aP < 0.05, ^bP < 0.01 vs T2DM/NAFLD.

Figure 3

Insulin receptor protein expression in rat liver tissues of each group. A: Insulin receptor (IR) expression was assessed by Western blot analysis; B: The results are shown as the ratio of IR to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) based on densitometry analysis. The values are expressed as mean ± SD (n = 7). ^bP < 0.01 vs T2DM/NAFLD. NC: Normal control; T2DM: Type 2 diabetes mellitus; NAFLD: Nonalcoholic fatty liver disease; gAd: Globular adiponectin.

Figure 4

Insulin receptor mRNA expression in rat liver tissues of each group. Insulin receptor (IR) mRNA expression was assessed by RT-PCR analysis. The results are shown as a ratio of IR to β-actin based on densitometry analysis. The values are expressed as mean ± SD (n = 7). ^bP < 0.01 vs T2DM/NAFLD. NC: Normal control; T2DM: Type 2 diabetes mellitus; NAFLD: Nonalcoholic fatty liver disease; gAd: Globular adiponectin.