Abstract
We explored the cascade effects of a high fat-carbohydrate diet (HFCD) and pioglitazone (an anti-diabetic therapy used to treat type 2 diabetes mellitus (T2DM)) on lipid profiles, oxidative stress/antioxidant, insulin, and inflammatory biomarkers in a rat model of insulin resistance. Sixty albino rats (80-90 g) were randomly divided into three dietary groups; 1) standard diet; 2) HFCD diet for 12 weeks to induce an in vivo model of insulin resistance; and 3) HFCD diet plus pioglitazone. Blood and tissue samples were taken to assess hepatic function, lipid profiles, oxidative biomarkers, malondialdehyde (MDA) levels, antioxidant defense biomarkers, including reduced glutathione (GSH), superoxide dismutase (SOD), and the inflammatory markers interleukin-6 (IL-6) and tumor necrotic factor (TNF-α). HFCD-fed rats had significantly (P≤0.05) increased serum triacylglycerol (TG), total cholesterol (TC), low-density lipoprotein (LDL), alanine transaminase (ALT), and bilirubin levels, but decreased high-density lipoprotein (HDL) levels compared with the normal group. Moreover, serum leptin, resistin, TNF-α, and IL-6 levels were increased significantly in HFCD animals compared with controls. Similarly, HFCD-induced insulin resistance caused antioxidant and cytokine disturbances, which are important therapy targets for pioglitazone. Importantly, administration of this drug ameliorated these changes, normalized leptin and resistin and inflammatory markers by reducing TNF-α levels. Metabolic cascades of elevated lipid profiles, oxidative stress, insulin, and inflammatory biomarkers are implicated in insulin resistance progression. HFCD induced metabolic cascades comprising hypertriglyceridemia, hyperglycemia, insulin resistance, obesity-associated hormones, and inflammatory biomarkers may be alleviated using pioglitazone.
Highlights
Excess dietary fat and carbohydrate disturbances are the main causes of metabolic disorders, especially hepatic steatosis, metabolic syndrome, type 2 diabetes mellitus (T2DM), and obesity [1]
The high fat-carbohydrate diet (HFCD) initiated a metabolic cascade of elevated lipid profiles, hypertriglyceridemia, hyperglycemia, oxidative stress, insulin, and inflammatory biomarkers implicated in insulin resistance and non-alcoholic fatty liver disease (NAFLD)
This cascade was broken at several stages of hyperglycemia, hypertriglyceridemia, oxidative stress, inflammation, and insulin resistance using pioglitazone
Summary
Excess dietary fat and carbohydrate disturbances are the main causes of metabolic disorders, especially hepatic steatosis, metabolic syndrome, type 2 diabetes mellitus (T2DM), and obesity [1]. Diabetes mellitus (DM) is a collection of metabolic syndromes represented by hyperglycemia, inadequate insulin synthesis, and improper responses to insulin [2]. 85–90% of diabetics have T2DM characterized by insulin resistance, meaning circulating insulin cannot bind to receptors thereby limiting downstream biochemical functions, i.e., glycolysis, glycogenesis, lipogenesis, and protein anabolism. Insulin resistance in muscle and liver is influenced by large fat deposits in extended adipose tissue bulk, thereby contributing to obesity [4]. Adipose tissue is the main energy source in the body, where resident macrophages secrete numerous proteins [6]
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