α-lipoic acid attenuates obesity-associated hippocampal neuroinflammation and increases the levels of brain-derived neurotrophic factor in ovariectomized rats fed a high-fat diet

Sep 7, 2013International journal of molecular medicine

Alpha-lipoic acid reduces brain inflammation linked to obesity and raises brain growth factor levels in female rats without ovaries on a high-fat diet

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Abstract

α-Lipoic acid treatment for 12 weeks significantly reduced body weight and improved lipid profiles in ovariectomized rats fed a high-fat diet.

Treatment with α-lipoic acid decreased serum total cholesterol and low-density lipoprotein cholesterol levels.
Levels of leptin and insulin resistance were also reduced in the treated rats.
Conversely, serum adiponectin and high-density lipoprotein cholesterol levels increased following α-lipoic acid administration.
In the hippocampus, the expression of brain-derived neurotrophic factor was significantly upregulated after treatment.
Inflammatory markers interleukin 6 and tumor necrosis factor-α showed decreased levels in response to α-lipoic acid.

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Overweight or obesity in post-menopausal women is known to induce metabolic disorders associated with neuroinflammation. α-lipoic acid (α-LA), which has been clinically used to treat diabetic peripheral neuropathy, has been found to exert anti-inflammatory and neuroprotective effects in patients with Alzheimer's disease (AD). In this study, to investigate the effects of α-LA on neuroinflammatory factors and the levels of hippocampal brain-derived neurotrophic factor (BDNF) in ovariectomized rats fed a high-fat diet (HFD), Wistar ovariectomized rats were fed HFD alone or HFD and treated with α-LA for 12 weeks. Metabolic parameters in serum were detected, real-time polymerase chain reaction (RT-PCR), western blot analysis and ELISA were used to evaluate the levels of inflammatory factors and BDNF in the hippocampus. α-LA markedly reduced body weight, the levels of serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), as well as the levels of leptin and insulin resistance in ovariectomized rats fed HFD. It also significantly increased the levels of serum adiponectin and high-density lipoprotein cholesterol (HDL-C). In the hippocampal tissues of ovariectomized rats fed HFD, the protein and mRNA expression of BDNF was upregulated following the administration of α-LA. Conversely, the levels of interleukin 6 (IL-6) and tumour necrosis factor-α (TNF-α) were decreased following treatment with α-LA. These findings demonstrate that α-LA significantly increases the expression of BDNF in the hippocampus of obese ovariectomized rats fed HFD, possibly by improving lipid metabolism, enhancing insulin sensitivity and reversing central inflammation.

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α-lipoic acid attenuates obesity-associated hippocampal neuroinflammation and increases the levels of brain-derived neurotrophic factor in ovariectomized rats fed a high-fat diet

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