Comparative anti-inflammatory and lipid-normalizing effects of metformin and omega-3 fatty acids through modulation of transcription factors in diabetic rats

Abstract

BackgroundEmerging evidence suggests beneficial effects of omega-3 fatty acids on diabetic complications. The present study compared the progressive effects of metformin and flax/fish oil on lipid metabolism, inflammatory markers, and liver and renal function test markers in streptozotocin-nicotinamide-induced diabetic rats.MethodsStreptozotocin-induced diabetic rats were randomized into control and four diabetic groups: streptozotocin (STZ), metformin (200 mg/kg body weight (b.w)/day (D)), flax and fish oil (500 mg/kg b.w/D).ResultsMetformin and flax and fish oil exhibited increased expression of transcription factor peroxisome proliferator-activated receptor γ while the treatment downregulated sterol regulatory element-binding protein 1 and nuclear factor kβ as compared to those of the STZ group. Apart from modulation of transcription factor expression, the expression of fatty acid synthase, long chain acyl CoA synthase, and malonyl-CoA-acyl carrier protein transacylase was lowered by flax/fish oil treatment. Serum cholesterol, triglycerides, and VLDL were also significantly reduced in the treatment groups as compared to those in the STZ group. Although pathological abnormalities were seen in the liver and kidneys of rats on metformin, no significant changes in liver/renal function markers were observed at day 15 and day 30 of the treatment groups. Flax/fish oil had protective effects toward pathological abnormalities in the liver and kidney. Flax/fish oil improved lipid profile and alkaline phosphatase at day 30 as compared to that at day 15.ConclusionsThe present study demonstrates potential beneficial effects of metformin and flax/fish oil intervention in improving serum lipid profile by regulating the expression of transcription factors and genes involved in lipid metabolism in diabetic rats. In addition, these interventions also lowered the expression of atherogenic cytokines. The protective effects of flax/fish oil are worth investigating in human subjects on metformin monotherapy.

Co-administration effects of aqueous extract of turnip leaf and metformin in diabetic rats

“…(2016) who reported metformin had not beneficial effects on elevated ALT levels in diabetic rats. 41 On the other hand, monotherapy with AETL significantly increased AST levels even more than diabetic animals while it reduced ALT levels efficiently. Likewise, similar results were observed in early study in which AETL has been administrated to diabetic rats at the same dose.…”

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“…The proteins encoded by different PPAR genes (PPARα, PPARδ, and PPARγ) have the ability to induce hepatic peroxisome proliferation in response to xenobiotic stimuli 50 and PPARγ is believed to play a central role in regulation of carbohydrate and lipid metabolism, fatty acid metabolism and the PPARs are also assumed to possess anti- inflammatory activity 51 . Dysregulation of PPAR isoforms contributes to the development of a wide range of liver diseases 52 . The majority of studies deal with PPARγ in diabetic and obese animals 53,54,55, but the mechanistic relationship of increase of PPARγ expression in hepatotoxicity remains unclear to date.…”

Effect of <i>Arthrospira maxima</i> and <i>Chlorella vulgaris</i> to Lipid Profile and Visceral Fat Index Alteration in Streptozotocin-Induced Hyperglycemia Rats

“…C. vulgaris can lower triglyceride levels better than A. maxima because the ratio of omega-6 / omega-3 to C. vulgaris is lower than A. maxima (Gonzalez-Periz et al, 2009;Zanwar et al, 2018) Previous studies have revealed that Arthrospira and Chlorella can reduce triglyceride levels (Jong-Yuh & Mei-Fen, 2005;Ou et al, 2012;Karima & Mulyati, 2019). The decrease of triglyceride levels may be influenced by omega-3 content in both microalgae (Ghadge et al, 2016). Chlorella is a good source of dietary fiber that affects lymphatic cholesterol and triglyceride absorption by increasing intestinal viscosity, changing the composition of bile acid pools or producing fermented products in the intestine (Ryu et al, 2014).…”

“…of STZ. Some previous studies used higher STZ dose variations to induce type 2 diabetes mellitus (Ghadge et al, 2016;Rouhi et al, 2017). Meanwhile, according to Radenkovic et al (2015), the most widely dose used to induce diabetes is 35-80 mg/kg b.w.…”

“…Increasing the utilization of peripheral glucose has the potential to reduce the production of fatty acids and triglycerides (Srinivasan et al, 2018). C. vulgaris can lower triglyceride levels better than A. maxima because the ratio of omega-6 / omega-3 to C. vulgaris is lower than A. maxima (Gonzalez-Periz et al, 2009;Zanwar et al, 2018) Previous studies have revealed that Arthrospira and Chlorella can reduce triglyceride levels (Jong-Yuh & Mei-Fen, 2005;Ou et al, 2012;Karima & Mulyati, 2019). The decrease of triglyceride levels may be influenced by omega-3 content in both microalgae (Ghadge et al, 2016).…”