Alpha-lipoic acid improves high-fat diet-induced hepatic steatosis by modulating the transcription factors SREBP-1, FoxO1 and Nrf2 via the SIRT1/LKB1/AMPK pathway

Background: The intricate relationship between type 2 diabetes mellitus (T2DM) and Alzheimer’s disease (AD) suggests that insulin is involved in modulating AD-related proteins. Alpha-lipoic acid (ALA) can improve insulin resistance (IR) in diabetic rats. However, the role of ALA in alleviating the cognitive decline of T2DM is not yet clear. This study examined the ameliorative effect of ALA on cognitive impairment, cerebral IR, and synaptic plasticity abnormalities in high-fat diet (HFD) plus streptozotocin (STZ) induced diabetic rats.Methods: The HFD/STZ-induced T2DM male Wistar rats were orally administered with ALA (50, 100, or 200 mg/kg BW) once a day for 13 weeks. Abilities of cognition were measured with a passive avoidance test and Morris water maze. Specimens of blood and brain were collected for biochemical analysis after the rats were sacrificed. Western blotting was used to determine protein expressions in the hippocampus and cortex in the insulin signaling pathways, long-term potentiation (LTP), and synaptic plasticity-related protein expressions.Results: Alpha-lipoic acid improved hyperinsulinemia and the higher levels of free fatty acids of the T2DM rats. Behavioral experiments showed that the administration of ALA improved cognitive impairment in HFD/STZ-induced T2DM rats. ALA ameliorated insulin-related pathway proteins [phosphoinositide 3-kinase (PI3K), phospho-protein kinase B (pAkt)/Akt, and insulin-degrading enzyme (IDE)] and the LTP pathway, as well as synaptic plasticity proteins (calmodulin-dependent protein kinase II, cyclic AMP response element-binding protein, and postsynaptic density protein-95) of the cerebral cortex or hippocampus in HFD/STZ-induced T2DM rats.Conclusion: Our findings suggested that ALA may ameliorate cognition impairment via alleviating cerebral IR improvement and cerebral synaptic plasticity in diabetic rats.

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Metformin Preserves Peripheral Nerve Damage with Comparable Effects to Alpha Lipoic Acid in Streptozotocin/High-Fat Diet Induced Diabetic Rats

Diabetes & Metabolism Journal ◽

10.4093/dmj.2019.0190 ◽

2020 ◽

Vol 44 (6) ◽

pp. 842-853 ◽

Cited By ~ 1

Author(s):

Sun Hee Kim ◽

Tae Sun Park ◽

Heung Yong Jin

Keyword(s):

Peripheral Nerve ◽

Lipoic Acid ◽

High Fat Diet ◽

Diabetic Rats ◽

Nerve Damage ◽

Alpha Lipoic Acid ◽

High Fat ◽

Peripheral Nerve Damage

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Biochemical study on the effect of alpha-lipoic acid on lipid metabolism of rats fed high fat diet

Benha Veterinary Medical Journal ◽

10.21608/bvmj.2015.32663 ◽

2015 ◽

Vol 28 (1) ◽

pp. 109-119 ◽

Cited By ~ 3

Author(s):

Samy Hussein ◽

Afaf Abdel-mageid ◽

Ahmed Abu-ghazalla

Keyword(s):

Lipid Metabolism ◽

Lipoic Acid ◽

High Fat Diet ◽

Biochemical Study ◽

Alpha Lipoic Acid ◽

High Fat

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Lipoic Acid Prevents High-Fat Diet-Induced Hepatic Steatosis in Goto Kakizaki Rats by Reducing Oxidative Stress Through Nrf2 Activation

International Journal of Molecular Sciences ◽

10.3390/ijms19092706 ◽

2018 ◽

Vol 19 (9) ◽

pp. 2706 ◽

Cited By ~ 9

Author(s):

Cristina Sena ◽

Maria Cipriano ◽

Maria Botelho ◽

Raquel Seiça

Keyword(s):

Oxidative Stress ◽

Type 2 Diabetes ◽

Liver Function ◽

Hepatic Steatosis ◽

Lipoic Acid ◽

High Fat Diet ◽

Control Group ◽

High Fat ◽

Tnf Α

Prevention of hepatic fat accumulation may be an important approach for liver diseases due to the increased relevance of hepatic steatosis in this field. This study was conducted to investigate the effects of the antioxidant α-lipoic acid (α-LA) on hepatic steatosis, hepatocellular function, and oxidative stress in a model of type 2 diabetes fed with a high fat diet (HFD). Goto-Kakizaki rats were randomly divided into four groups. The first group received only a standard rat diet (control GK) including groups 2 (HFD), 3 (vehicle group), and 4 (α-LA group), which were given HFD, ad libitum during three months. Wistar rats are the non-diabetic control group. Carbohydrate and lipid metabolism, liver function, plasma and liver tissue malondialdehyde (MDA), liver GSH, tumor necrosis factor-α (TNF-α) and nuclear factor E2 (erythroid-derived 2)-related factor-2 (Nrf2) levels were assessed in the different groups. Liver function was assessed using quantitative hepatobiliary scintigraphy, serum aspartate, and alanine aminotransferases (AST, ALT), alkaline phosphatase, gamma-glutamyltranspeptidase, and bilirubin levels. Histopathologically steatosis and fibrosis were evaluated. Type 2 diabetic animals fed with HFD showed a marked hepatic steatosis and a diminished hepatic extraction fraction and both were fully prevented with α-LA. Plasma and liver tissue MDA and hepatic TNF-α levels were significantly higher in the HFD group when compared with the control group and significantly lower in the α-LA group. Systemic and hepatic cholesterol, triglycerides, and serum uric acid levels were higher in hyperlipidemic GK rats and fully prevented with α-LA. In addition, nuclear Nrf2 activity was significantly diminished in GK rats and significantly augmented after α-LA treatment. In conclusion, α-LA strikingly ameliorates steatosis in this animal model of diabetes fed with HFD by decrementing the inflammatory marker TNF-α and reducing oxidative stress. α-LA might be considered a useful therapeutic tool to prevent hepatic steatosis by incrementing antioxidant defense systems through Nrf2 and consequently decreasing oxidative stress and inflammation in type 2 diabetes.

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Ginsenoside Rg2 inhibits adipogenesis in 3T3-L1 preadipocytes and suppresses obesity in high-fat-diet-induced obese mice through the AMPK pathway

Food & Function ◽

10.1039/c9fo00027e ◽

2019 ◽

Vol 10 (6) ◽

pp. 3603-3614 ◽

Cited By ~ 11

Author(s):

Huimin Liu ◽

Meihong Liu ◽

Zhibo Jin ◽

Sanabil Yaqoob ◽

Mingzhu Zheng ◽

...

Keyword(s):

Transcription Factors ◽

High Fat Diet ◽

Obese Mice ◽

High Fat ◽

Ampk Pathway

Rg2-induced activation of AMPK reduced the expression of adipogenic transcription factors, and regulated the lipogenic and lipolysis genes, thus inhibiting adipogenesis.

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