Dietary Α-lipoic Acid Research Articles

Reciprocal effects of α-lipoic acid on adenosine monophosphate-activated protein kinase activity in obesity induced by ovariectomy in rats

Adenosine monophosphate (AMP)-activated protein kinase (AMPK) plays an important role in regulating whole-body energy homeostasis. The aim of this study was to investigate dietary α-lipoic acid (α-LA) supplementation on the activation of AMPK in both central and peripheral tissues in obese rats induced by ovariectomy. Ovariectomized (Ovx) rats were treated with α-LA (200 mg/kg) 3 to 10 weeks after surgery. Body weight, food intake, fat mass, phosphorylated AMPKα (pAMPKα), and phosphorylated acetyl-CoA carboxylase (ACC) protein expression in both the hypothalamus and white adipose tissue (WAT) as well as plasma leptin and adiponectin levels were measured in rats after either Ovx or sham operations. Compared with control rats, ovariectomy led to increased body weight, food intake, and WAT mass 2 to 10 weeks after surgery. Furthermore, plasma leptin and adiponectin levels as well as hypothalamic pAMPKα expression were significantly increased after ovariectomy, accompanied by a reduction in pAMPKα expression in WAT after ovariectomy. However, after treatment with α-LA, the elevation of leptin and adiponectin levels and the activation of hypothalamic AMPKα and ACC, as induced by ovariectomy, were significantly suppressed. Meanwhile, decreased fat mass and increased pAMPKα and phosphorylated ACC expression in the WAT were observed in Ovx rats treated with α-LA. α-LA significantly decreased appetite and fat accumulation, possibly through the regulation of central and peripheral AMPK activities in rats. Therefore, this study provides a rationale for the therapeutic use of α-LA for obesity in postmenopausal women.

Effects of dietary α-lipoic acid on the growth and antioxidative responses of juvenile abalone Haliotis discus hannai Ino

A feeding experiment was conducted to determine the effects of α-lipoic acid (LA) on the growth and antioxidative responses of juvenile abalone Haliotis discus hannai Ino. Six purified diets supplemented with 0, 200, 400, 800, 1600 and 3200 mg kg−1 of LA, respectively, were fed to abalone for 16 weeks in a flow-through water system. The results showed that the weight gain ratio (WGR) increased with the dietary LA levels, and reached the highest value in the group with 800 mg kg−1 dietary LA supplement. Glutathione peroxidase activity in the 800 mg kg−1 dietary LA group was significantly higher than that in the dietary LA-deficient (0 mg kg−1) group. Superoxide dismutase activities in the 200, 400 and 800 mg kg−1 groups were significantly increased. Supplements of 200, 400 and 800 mg kg−1 dietary LA elevated the total antioxidative capacity significantly. The glutathione level in the hepatopancreas increased significantly with the dietary LA supplements in a dose-dependent manner (except for the 200 mg kg−1 group). Catalase and malondialdehyde in the hepatopancreas were not significantly affected by dietary LA. In conclusion, dietary LA promoted the growth and stimulated the antioxidative defence capacity of abalone. Based on the data of WGR, the optimal dietary LA supplement for juvenile abalone was found to be 709 mg kg−1 using piece-wise linear analysis.

Dietary lipoic acid-dependent changes in the activity and mRNA levels of hepatic lipogenic enzymes in rats

Effects of dietary alpha-lipoic acid on hepatic and serum lipid concentrations and the activity and mRNA levels of lipogenic enzymes were examined in rats. Rats were fed experimental diets containing varying amounts of lipoic acid (0, 1, 2.5, 5 g/kg) for 21 d. Lipoic acid profoundly decreased serum and liver concentrations of TAG, and also lowered serum concentrations of phospholipid and NEFA, and the concentration of cholesterol in the liver. A hypoglycaemic effect of this compound was also observed. Lipoic acid dose-dependently decreased the activity and mRNA levels of fatty acid synthase, ATP-citrate lyase, glucose 6-phosphate dehydrogenase, malic enzyme and pyruvate kinase in the liver despite that reductions were considerably attenuated in the NADPH-producing enzymes. This compound also dose-dependently lowered the mRNA levels of spot 14, adiponutrin, stearoyl-CoA desaturase 1, and Delta5- and Delta6-desaturases. In addition, lipoic acid dose-dependently lowered serum concentrations of insulin and leptin, but increased those of adiponectin. Lipoic acid appeared to reduce hepatic lipogenesis and hence decreases serum and liver lipid levels. Alterations in serum concentrations of insulin and (or) adiponectin may trigger this consequence.

Effects of α-lipoic and ascorbic acid on the muscle and brain fatty acids and antioxidant profile of the South American pacu Piaractus mesopotamicus

The effects of dietary α-lipoic acid (LA) and vitamin C on the fatty acid (FA) composition in the brain and muscle and vitamins E and C levels in the brain were studied in the fish Piaractus mesopotamicus. A two-factorial design, where diets were devoid or supplemented with ascorbate (500 mg AA kg−1) and/or lipoic acid (1000 mg kg−1), was used. The levels of eicosapentaenoic acid (20:5n−3, EPA) increased (P<0.01) in muscle polar lipids (PL) in LA groups (6.93%±0.43 vs. 5.83%±0.40 and 6.68%±0.53 vs. 6.00%±0.39), and the same trend was also seen in the brain, however not significant. These changes are suggested to be caused by a change in lipid metabolism rather than being a direct effect of protection by LA against lipid peroxidation. No interaction of vitamin C and LA neither effects of LA on vitamin E (15.1–19.2 mg α-tocopherol g−1 tissue) or vitamin C (total AA, 41.7–89.8 μg g−1 tissue) in brain was detected.

α-Lipoic acid-enrichment partially reverses tissue ascorbic acid depletion in pacu (Piaractus mesopotamicus) fed vitamin C-devoid diets

Effects of dietary α-lipoic acid (LA) and ascorbic acid (AA) on the growth, tissue vitamin C and tocopherol (vitamin E) levels, and malondialdehyde levels were examined in the tropical fish pacu, Piaractus mesopotamicus. Pacu juveniles were fed one of four casein-gelatin-based diets for 8 weeks: with 0.05% AA and 0.1% LA (+AA+LA), with AA and without LA (+AA–LA), without AA and with LA (−AA+LA), and without AA and LA (−AA−LA). When the fish received quantities of feed equal to 1.9–2.5% of its body weight, growth was not influenced, regardless of the presence of AA or LA throughout most of the experimental period. Growth was, however, slightly but significantly lower at week 8 in the AA-deficient/LA-supplemented group. An AA-deficient diet caused a highly significant reduction in both total AA and dehydroascorbic acid content in the liver and gill tissues. This reduction of tissue AA concentrations was reversed in a significant manner by LA (antioxidant-sparing effect). The 8-week-long vitamin C deprivation was sufficient to initiate the reduction in tissue ascorbic acid; however, total ascorbate in the liver of fish in the (−)AA/(+)LA group was 127.7±54.3 nmol g−1 tissue, whereas it was 28.6±26.3 nmol g−1 in the (−)AA/(−)LA group, a 4.4-fold difference. This mitigating effect of the addition of the endogenous antioxidant LA to the diet indicates that LA exerts a vitamin C-sparing effect in teleost fish that by far exceeds the phenomena demonstrated in non-scurvy-prone mammals. There was no difference among the different diet groups for vitamin E and malondialdehyde levels in the liver. These results suggest that LA is a potent substance for the prevention of AA deficiency in cultured fishes. The optimal dietary level of LA needs to be determined in the light of the slight reduction in body weight gain after 8 weeks of feeding in the absence of AA.

α-Lipoic Acid Prevents the Increase in Atherosclerosis Induced by Diabetes in Apolipoprotein E–Deficient Mice Fed High-Fat/Low-Cholesterol Diet

Considerable evidence indicates that hyperglycemia increases oxidative stress and contributes to the increased incidence of atherosclerosis and cardiovascular complications in diabetic patients. To examine the effect of alpha-lipoic acid, a potent natural antioxidant, on atherosclerosis in diabetic mice, 3-month-old apolipoprotein (apo) E-deficient (apoE(-/-)) mice were made diabetic by administering streptozotocin (STZ). At 4 weeks after starting the STZ administration, a high-fat diet with or without alpha-lipoic acid (1.65 g/kg) was given to the mice and to nondiabetic apoE(-/-) controls. At 20 weeks, markers of oxidative stress were significantly lower in both the diabetic apoE(-/-) mice and their nondiabetic apoE(-/-) controls with alpha-lipoic acid supplement than in those without it. Remarkably, alpha-lipoic acid completely prevented the increase in plasma total cholesterol, atherosclerotic lesions, and the general deterioration of health caused by diabetes. These protective effects of alpha-lipoic acid were accompanied by a reduction of plasma glucose and an accelerated recovery of insulin-producing cells in the pancreas, suggesting that part of its effects are attributable to protecting pancreatic beta-cells from damage. Our results suggest that dietary alpha-lipoic acid is a promising protective agent for reducing cardiovascular complications of diabetes.

Chronic dietary α-lipoic acid reduces deficits in hippocampal memory of aged Tg2576 mice

Oxidative stress may play a key role in Alzheimer's disease (AD) neuropathology. Here, the effects of the antioxidant, α-lipoic acid (ALA) were tested on the Tg2576 mouse, a transgenic model of cerebral amyloidosis associated with AD. Ten-month old Tg2576 and wild type mice were fed an ALA-containing diet (0.1%) or control diet for 6 months and then assessed for the influence of diet on memory and neuropathology. ALA-treated Tg2576 mice exhibited significantly improved learning, and memory retention in the Morris water maze task compared to untreated Tg2576 mice. Twenty-four hours after contextual fear conditioning, untreated Tg2576 mice exhibited significantly impaired context-dependent freezing. ALA-treated Tg2576 mice exhibited significantly more context freezing than the untreated Tg2576 mice. Assessment of brain soluble and insoluble β-amyloid levels revealed no differences between ALA-treated and untreated Tg2576 mice. Brain levels of nitrotyrosine, a marker of nitrative stress, were elevated in Tg2576 mice, while F2 isoprostanes and neuroprostanes, oxidative stress markers, were not elevated in the Tg2576 mice relative to wild type. These data indicate that chronic dietary ALA can reduce hippocampal-dependent memory deficits of Tg2576 mice without affecting β-amyloid levels or plaque deposition.

Effect of dietary α-lipoic acid on growth, body composition, muscle pH, and AMP-activated protein kinase phosphorylation in mice1

The effects of alpha-lipoic acid (ALA) on the growth, body composition, postmortem AMP-activated protein kinase (AMPK) activation, and 24-h muscle pH were investigated. Thirty male C57BL/6J mice were fed diets containing 0, 0.5, or 1.0% ALA (DM basis). At the end of the 3-wk feeding trial, carcass weights decreased (P < 0.05) 14 and 30% for mice fed 0.5 and 1.0% ALA, respectively, compared with the 0% group, with decreases in BW as the levels of dietary ALA increased. This change in carcass weight occurred because carcass fat content for mice receiving 0.5 and 1.0% ALA was 7.32 and 8.09% lower (P < 0.05), respectively, than for the 0% ALA treatment, and because gonadal fat decreased (P < 0.05) 85% in mice fed 1.0% ALA compared with those fed 0% ALA. Dietary ALA caused a slight increase (P < 0.05) in carcass moisture content, with no (P = 0.07) effect on protein and ash content. Furthermore, ALA supplement decreased (P < 0.05) ADFI (DM basis) from 4.3 g/d for 0% ALA-fed mice to 3.4 g/d for 1.0% ALA-fed mice. At 20 min postmortem, pH was greater (P < 0.05) in muscle of mice fed 1.0% ALA than in muscle of mice fed 0% ALA. Ultimate (24-h) pH values differed (P < 0.05) among treatments, and mean values were 5.83, 6.08, and 6.29 for 0, 0.5, and 1.0% ALA, respectively. Phosphorylation of AMPK alpha subunit at Thr172, an indicator of AMPK activation, was decreased (P < 0.05) in muscle of ALA-treated mice at 20 min postmortem. Because AMPK has a crucial role in the control of glycolysis, the reduction in AMPK activation decreases glycolysis, and thereby increases the ultimate pH of postmortem muscle. In summary, dietary ALA supplement can decrease fat accumulation in mice, and because ALA increased muscle pH at 20 min and 24 h postmortem, these results suggest that dietary ALA supplementation might decrease carcass fatness and prevent the development of PSE pork and poultry. However, further research is required to test the effects of ALA in swine and poultry.

Effects of dietary α-lipoic acid on glycolysis of postmortem muscle

The effects of dietary α-lipoic acid (α-LA) on the pH value, AMP-activated protein kinase (AMPK) activation, and the activities of glycogen phosphorylase and pyruvate kinase in postmortem muscle were investigated. Eighteen C57BL/6J mice were fed diets containing 0%, 0.5%, and 1.0% α-LA. At the end of 2-week feeding trial, the mice were killed and longissimus muscles were sampled at 0-, 1-, and 24-h postmortem for pH determination and enzyme assay. The results showed that dietary α-LA treatment significantly slowed down the decrease of pH values in postmortem muscle. The ultimate pH values in postmortem muscle of mice receiving 0.5% and 1.0% α-LA treatments were 6.40 and 6.63, respectively, significantly higher than that (6.21) of no α-LA treatment ( p < 0.05). AMPK was activated at the early postmortem stage. Dietary α-LA can suppress the activation of AMPK in postmortem muscle. At 1- and 24-h postmortem, activities of AMPK were much lower in postmortem muscle of mice receiving 0.5% and 1.0% α-LA treatments than that with no α-LA treatment. Between these two dietary α-LA treatments, however, no difference in AMPK activity was observed, indicating that 0.5% dietary α-LA is enough to suppress AMPK in postmortem muscle. Similar to AMPK, glycogen phosphorylase activity was higher in the treatment without dietary α-LA than those with 0.5% and 1.0% dietary α-LA supplements. No difference in the activity of glycogen phosphorylase was observed between the 0.5% and 1.0% dietary α-LA treatments. Dietary α-LA had no significant influence on the activity of pyruvate kinase in postmortem muscle. All these results indicate that AMPK plays a role in glycolysis in postmortem muscle. Dietary α-LA supplementation can suppress the activation of AMPK in postmortem muscle, down-regulate the activity of glycogen phosphorylase, resulting in a higher ultimate pH values in postmortem muscle. Therefore, dietary α-LA supplementation is a potential way to reduce the incidence of pale, soft, exudative (PSE) meat.

Dietary alpha-lipoic acid supplementation lowers blood pressure in spontaneously hypertensive rats.

In spontaneously hypertensive rats (SHRs), excess endogenous aldehydes bind sulfhydryl groups of membrane proteins, altering membrane Ca2+ channels and increasing cytosolic free calcium and blood pressure. The thiol compound, N-acetyl cysteine, normalizes elevated blood pressure in SHRs by binding excess endogenous aldehydes and normalizing membrane Ca2+ channels and cytosolic free calcium. The aim of the present study was to investigate whether a dietary supplementation of an endogenous fatty acid, alpha-lipoic acid, another thiol compound that is known to increase tissue cysteine and glutathione, can lower blood pressure and normalize associated biochemical and histopathological changes in SHRs. Starting at 12 weeks of age, animals were divided into three groups of six animals each. Animals in the Wistar- Kyoto (WKY) rat control group and the SHR control group were given a normal diet, and the SHR-lipoic acid group was given a diet supplemented with lipoic acid (500 mg/kg feed) for the next 9 weeks. After 9 weeks, systolic blood pressure, platelet [Ca2+]i, plasma insulin and liver, kidney and aortic aldehyde conjugates were significantly higher in SHR controls as compared with WKY rat controls and the SHR lipoic acid group. SHR controls also showed smooth muscle cell hyperplasia in the small arteries and arterioles of the kidneys. Dietary alpha-lipoic acid supplementation in SHRs lowered the systolic blood pressure, cytosolic [Ca2+]i, blood glucose and insulin levels, and tissue aldehyde conjugates, and attenuated adverse renal vascular changes.