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Published on: August 14, 2013
Synergistic Effect of Omega-3 Fatty Acids and Oral-Hypoglycemic Drug on Lipid Normalization through Modulation of
Suresh Khadke1, Pallavi Mandave1, Aniket Kuvalekar1
1Interactive Research School for Health Affairs, Bharati Vidyapeeth, Deemed to be University, Pune-Satara Road, Pune 411043, Maharashtra, India.
Abstract:
Type 2 diabetes mellitus, which an outcome of impaired insulin action and its secretion, is concomitantly associated with lipid abnormalities. The study was designed to evaluate the combinational effect of omega-3 fatty acids (flax and fish oil) and glibenclamide on abnormal lipid profiles, increased blood glucose, and impaired liver and kidney functions in a high fat diet with low streptozotocin (STZ)-induced diabetic rats, including its probable mechanism of action. The male Wistar rats (n = 48) were distributed into eight groups. All animal groups except the healthy received a high fat diet (HFD) for 90 days. Further, diabetes was developed by low dose STZ (35 mg/kg). Diabetic animals received, omega-3 fatty acids (500 mg/kg), along with glibenclamide (0.25 mg/kg). Both flax and fish oil intervention decreased (p ≤ 0.001) serum triglycerides and very low density lipoprotein and elevated (p ≤ 0.001) high density lipoprotein levels in diabetic rats. Total cholesterol and low-density lipoprotein level was decreased (p ≤ 0.001) in fish oil-treated rats. However, it remained unaffected in the flax oil treatment group. Both flax and fish oil intervention downregulate the expression of fatty acid metabolism genes, transcription factors (sterol regulatory element-binding proteins-1c and nuclear factor-κβ), and their regulatory genes i.e., acetyl-coA carboxylase alpha, fatty acid synthase, and tumor necrosis factors-α. The peroxisome proliferator-activated receptor gamma gene expression was upregulated (p ≤ 0.001) in the fish oil treatment group. Whereas, carnitine palmitoyltransferase 1 and fatty acid binding protein gene expression were upregulated (p ≤ 0.001) in both flax and fish oil intervention group.
Insights
Omega-3 fatty acids from flax and fish oil, combined with glibenclamide, improve lipid profiles and blood glucose in diabetic rats. These interventions also modulate key genes involved in fatty acid metabolism and inflammation.
Area of Science:
- Biochemistry
- Pharmacology
- Endocrinology
Background:
- Type 2 diabetes mellitus is characterized by impaired insulin secretion and action, often accompanied by dyslipidemia.
- High-fat diets and streptozotocin (STZ) are commonly used to induce diabetic conditions in animal models for research purposes.
Purpose of the Study:
- To investigate the combined effects of omega-3 fatty acids (flaxseed and fish oil) and glibenclamide on lipid profiles, blood glucose, and organ function in a rat model of type 2 diabetes.
- To elucidate the underlying molecular mechanisms, including gene expression changes, associated with these interventions.
Main Methods:
- Male Wistar rats were fed a high-fat diet (HFD) for 90 days, followed by induction of diabetes using a low dose of streptozotocin (STZ).
- Diabetic rats received omega-3 fatty acids (flax or fish oil, 500 mg/kg) in combination with glibenclamide (0.25 mg/kg).
- Serum lipid profiles, blood glucose levels, liver and kidney functions, and the expression of key genes related to fatty acid metabolism and inflammation were analyzed.
Main Results:
- Both flax and fish oil significantly reduced serum triglycerides and very-low-density lipoprotein (VLDL) while increasing high-density lipoprotein (HDL) levels.
- Fish oil, but not flax oil, significantly decreased total cholesterol and low-density lipoprotein (LDL) levels.
- Interventions downregulated genes involved in fatty acid metabolism (e.g., ACC, FAS) and inflammatory markers (e.g., NF-κβ, TNF-α).
- Fish oil upregulated PPARγ, while both oils upregulated CPT1 and FABP gene expression.
Conclusions:
- Combination therapy with omega-3 fatty acids and glibenclamide demonstrates significant benefits in managing dyslipidemia and hyperglycemia in a type 2 diabetes rat model.
- These effects are mediated through the modulation of fatty acid metabolism and inflammatory pathways at the gene expression level.
- Fish oil shows a broader impact on lipid profile improvement compared to flax oil in this model.
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