Effects of combination of obesity, diabetes, and hypoxia on inflammatory regulating genes and cytokines in rat pancreatic tissues and serum

Background. Obesity and diabetes are becoming increasingly prevalent around the world. Inflammation, oxidative stress, insulin resistance, and glucose intolerance are linked to both obesity and type 2 diabetes, and these disorders are becoming major public health issues globally. Methods. This study evaluated the effects of obesity, diabetes, and hypoxia on the levels of pro- and anti-inflammatory cytokines in rats. We divided 120 Wistar rats in two groups, male and female, each including six subgroups: control (CTRL), obese (high-fat diet (HFD)), diabetic (streptozotocin (STZ)-treated), hypoxic (HYX), obese + diabetic (HFD/STZ), and obese + diabetic + hypoxic (HFD/STZ/HYX). We examined the levels of tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, IL10, and leptin in pancreatic tissues and serum. Results. No significant difference was observed in serum levels of cholesterol, triglycerides, and low-density lipoprotein (LDL) between HYX and CTRL in either sex. However, they were significantly increased, whereas high-density lipoprotein (HDL) was significantly decreased in HFD, STZ, HFD/STZ, and HFD/STZ/HPX compared with CTRL in both sexes. The expression of Tnf-alpha, Il6, and Lep was significantly upregulated in all subgroups compared with CTRL in both sexes. STZ and HYX showed no significant differences in the expression of these genes between sexes, whereas Tnf-alpha and Il6 were upregulated in male HFD, HFD/STZ, and HFD/STZ/HYX compared with females. Protein levels showed similar patterns. Combination subgroups, either in the absence or presence of hypoxia, frequently exhibited severe necrosis of endocrine components in pancreatic lobules. The combination of obesity, diabetes, and hypoxia was associated with inflammation, which was verified at the histopathological level.