Lipoic acid entrains the hepatic circadian clock and lipid metabolic proteins that have been desynchronized with advanced age

Keith, Dove J.; Finlay, Liam; Butler, Jane; Gómez, Luis A.; Smith, Eric; Moreau, Régis; Hagen, Tory M.

doi:10.1016/j.bbrc.2014.05.112

Cited by 5 publications

(5 citation statements)

References 37 publications

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“…Previous studies have found other agents that could improve aging-related metabolic dysfunction. [36][37][38] In the present study, we have confirmed the beneficial effect of rutin for the intervention of aging-related metabolic disorders. Since rutin is an important constituent in many kinds of human food materials, it provides a potent option for the intervention of metabolic syndrome in old individuals.…”

Section: Discussionsupporting

confidence: 82%

Rutin protects against aging-related metabolic dysfunction

Chen

Feng

et al. 2016

Food Funct.

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Aging is a complex process which is accompanied by multiple related chronic diseases. Among them, metabolic dysfunction is one of the most important aging-related disorders. In the present study, we aimed to investigate the effect of rutin on aging-related metabolic dysfunction. We found that the increase of fasting blood glucose, insulin levels, blood pressure and HOMA-IR in aged rats was significantly inhibited by rutin. In addition, rutin improved glucose and insulin tolerance in aged rats, as reflected by decreased glucose level in IPGTT and IPITT test. Rutin treatment notably increased Akt and IRS-1 phosphorylation in the livers of old rats. The increase of inflammatory markers, such as IL-1β and TNFα, was prevented by the rutin administration. Moreover, in circulation and livers of old rats, rutin treatment significantly decreased the content of TG. Rutin also inhibited the increase of serum AST and ALT levels. Furthermore, rutin treatment markedly inhibited aging-related mitochondrial dysfunction, ER stress, and oxidative stress, as evidenced by increased oxygen consumption rate and activities of Na(+)/K(+)-ATPase and Ca2(+)-ATPase, decreased expression of ATF3 and GRP78, decreased level of MDA, increased content of GSH and enhanced activity of SOD in aged rats. We show that the administration of rutin could effectively improve aging-related metabolic dysfunction. The amelioration of inflammation, lipid accumulation, mitochondrial dysfunction, ER stress, and oxidative stress may be involved in the effect of rutin on aging-related metabolic dysfunction. These findings provide novel insights into the potential use of rutin in the intervention of aging and its related metabolic diseases.

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Section: Discussionsupporting

confidence: 82%

Rutin protects against aging-related metabolic dysfunction

Chen

Feng

et al. 2016

Food Funct.

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“…Alternatively, although the αLA group also displayed a reduction in hepatic TG content, the hepatic FA profile shifted in the opposite direction as the PS-fed animals with a reduction in saturated FA and an increase in long chain PUFA. Furthermore, with a reduction in the 16:0/18:2n-6 ratio and a reduced FAS and ACC mRNA expression, TG reductions in response to αLA are likely through a direct lowering of hepatic lipogenesis, as supported by previous work [48,49]. Given the opposite directions of FAS and ACC expression following PS and αLA supplementation, it may not be surprising that the TG lowering response in the combination group was not greater than either therapy alone.…”

Section: Discussionsupporting

confidence: 53%

Complementary Cholesterol-Lowering Response of a Phytosterol/α-Lipoic Acid Combination in Obese Zucker Rats

Rideout

Carrier

Wen

et al. 2015

Journal of Dietary Supplements

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To investigate the cholesterol-lowering effectiveness of a phytosterol/α-lipoic acid (PS/αLA) therapy, thirty-two male Zucker rats were randomly assigned to 1 of 4 diets for 30 days: (i) high fat diet (HF, 40% energy from fat); (ii) HF diet supplemented with 3% phytosterols; (iii) HF diet supplemented with 0.25% αLA; or (iv) HF diet supplemented with PS (3%) and αLA (0.25%, PS/αLA). Compared with the HF diet, combination PS/αLA proved more effective in reducing non-HDL cholesterol (−55%) than either the PS (−24%) or the αLA (−25%) therapies alone. PS supplementation did not affect LDL particle number, however, αLA supplementation reduced LDL particle number when supplemented alone (−47%) or in combination with PS (−54%). Compared with the HF-fed animals, evidence of increased HDL-particle number was evident in all treatment groups to a similar extent (21–22%). PS-mediated interruption of intestinal cholesterol absorption was evident by increased fecal cholesterol loss (52%) and compensatory increase in HMG-CoA reductase mRNA (1.6 fold of HF), however, αLA supplementation did not affect fecal cholesterol loss. Hepatic mRNA and protein expression patterns suggested that αLA modulated multiple aspects of cholesterol homeostasis including reduced synthesis (HMG-CoA reductase mRNA, 0.7 fold of HF), reduced bile acid synthesis (CYP7a1 expression, 0.17 of HF), and increased cholesterol clearance (reduced PCSK9 mRNA, 0.5 fold of HF; increased LDLr protein, 2 fold of HF). Taken together, this data suggests that PS and αLA work through unique and complementary mechanisms to provide a superior and more comprehensive cholesterol lowering response than either therapy alone.

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“…Suppression of lncRNA expression caused significant overexpression of miR-146b (e). **, p-value < 0.01; ****, p-value < 0.0001. biosynthesis of TG (Keith et al, 2014), as a gene target for lncRNA based on a recent study (Chen et al, 2023). In the TG synthesis pathway, a number of enzymes including glycerol-3-phosphate acyltransferase and AGPAT2 are involved in the reactions of lysophospholipid acid, phospholipic acid and glycerol diester successively generated from glycerol triphosphate (Sahini & Borlak, 2014).…”

Section: Discussionmentioning

confidence: 99%

“…AGPAT2 has been reported to be involved in lipid metabolism in chickens, particularly in glycerolipid metabolism, glycerophospholipid metabolism and metabolic pathways, some of which are described as the main classic lipid metabolism signaling pathways (Doran et al., 2008; Gan et al., 2017; Yang et al., 2019). In fact, the current investigation considered AGPAT2 , a key rate‐limiting enzyme that belongs to the glycerol triphosphate pathway of de novo biosynthesis of TG (Keith et al., 2014), as a gene target for lncRNA based on a recent study (Chen et al., 2023). In the TG synthesis pathway, a number of enzymes including glycerol‐3‐phosphate acyltransferase and AGPAT2 are involved in the reactions of lysophospholipid acid, phospholipic acid and glycerol diester successively generated from glycerol triphosphate (Sahini & Borlak, 2014).…”

Section: Discussionmentioning

confidence: 99%

LncRNAENSGALG00000021686 regulates fat metabolism in chicken hepatocytes via miR‐146b/AGPAT2 pathway

Xing,

2024

Animal Genetics

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The liver contributes to lipid metabolism as the hub of fat synthesis. Long non‐coding RNAs (lncRNAs) are considered the regulators of cellular processes. Since LncRNA ENSGALG00000021686 (lncRNA 21 686) has been described as a regulator of lipid metabolism, the present study aimed to clarify the role of lncRNA 21 686 in chicken hepatocytes’ lipid metabolism. Thirty‐two chickens were divided into four groups and were treated with diets containing different amounts of fat, and the hepatic expression of lncRNA 21 686 and miR‐146b along with the levels of proteins involved in the regulation of fat metabolism, lipid indices and oxidative stress were measured. Moreover, primary chicken hepatocytes were transfected with lncRNA 21 686 small interfering RNA or microRNA (miRNA, miR)‐146b mimics to measure the consequences of suppressing lncRNA or inducing miRNA expression on the levels of proteins involved in fat metabolism and stress markers. The results showed that the high‐fat diet modulated the expression of lncRNA 21 686 and miR‐146b (p‐value < 0.001). Moreover, there was a significant increase in 1‐acyl‐sn‐glycerol‐3‐phosphate acyltransferase 2 (AGPAT2) gene expression and protein levels and modulated fat‐related markers. Furthermore, the results showed that lncRNA 21 686 suppression reduced the expression of AGPAT2 and its downstream proteins (p‐value < 0.05). Overexpression of miR‐146b regulated fat metabolism indicator expression. Transfection experiments revealed that lncRNA 21 686 suppression increased miR‐146b expression. The findings suggested a novel mechanism containing lncRNA 21 686/miR‐146b/AGPAT2 in the regulation of fat metabolism in chicken hepatocytes.

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Lipoic acid entrains the hepatic circadian clock and lipid metabolic proteins that have been desynchronized with advanced age

Cited by 5 publications

References 37 publications

Rutin protects against aging-related metabolic dysfunction

Rutin protects against aging-related metabolic dysfunction

Complementary Cholesterol-Lowering Response of a Phytosterol/α-Lipoic Acid Combination in Obese Zucker Rats

LncRNAENSGALG00000021686 regulates fat metabolism in chicken hepatocytes via miR‐146b/AGPAT2 pathway

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