Vitamin K2 Enhances Fat Degradation to Improve the Survival of C. elegans

Abstract

The beneficial effects of vitamin K (VK) on various chronic age-related syndromes have generally been considered dependent on its antioxidant effects. However, due to the distinct bioavailability and biological activities of VKs, exactly which of these activities and by what mechanisms they might act still need to be elucidated. In this study, we found that VK2 can extend the lifespan of C. elegans and improve the resistance to pathogen infection, heat stress and H2O2-induced inner oxidative stress. Importantly, the roles of VK2 on aging and stress resistance were shown to be dependent on enhanced fat metabolism and not due to its antioxidant effects. Moreover, the genes related to fat metabolism that were up-regulated following VK2 treatment play key roles in improving survival. Obesity is a leading risk factor for developing T2DM, and taking VKs has been previously considered to improve the insulin sensitivity associated with obesity and T2DM risk. However, our results showed that VK2 can significantly influence the expression of genes related to fat metabolism, including those that regulate fatty acid elongation, desaturation, and synthesis of fatty acid-CoA. VK2 enhanced the fatty acid β-oxidation activity in peroxisome to degrade and digest fatty acid-CoA. Our study implies that VK2 can enhance fat degradation and digestion to improve survival, supporting the effectiveness of VK2-based medical treatments. VK2 is mainly produced by gut bacteria, suggesting that VK2 might facilitate communication between the gut microbiota and the host intestinal cells to influence fat metabolism.

Reduction of neutral lipid reservoirs, bioconversion and untargeted metabolomics reveal distinct roles for vitamin K isoforms on lipid metabolism

“…25 In the Caenorhabditis elegans model, the vitamin K2 regulated fat metabolism genes; K2 enhanced fat degradation and digestion, and in particular fatty acid β-oxidation (fatty acid CoA synthetase family – acs-18 , acyl-coenzyme A oxidase – acox-1.2 , Δ9-fatty acid desaturase – fat-5 , fatty acid elongase – elo-2 , 3-hydroxyacyl–CoA dehydratase 1 – hacd-1 , acyl CoA dehydrogenase – acdh-8 ). 26 In concordance, data confirmed a lipid reducing activity of vitamin K2 across various organisms with huge evolutionary distance on the phylogenetic tree ( C. elegans , D. rerio , R. norvegicus ), pointing to a similar interspecies response to the exposure of this vitamin.…”

Anti-Aging Activity and Modes of Action of Compounds from Natural Food Sources

“…An increase in the intake of dietary vitamin K was associated with better cognitive function scores in an older adult Mediterranean population with high cardiovascular risk [248] and in adults with chronic kidney disease [249]. Recently, vitamin K2 was reported to extend the lifespan of C. elegans and improve the resistance to pathogenic infection, heat stress and H 2 O 2 -induced inner oxidative stress [214]. Interestingly, the roles of vitamin K2 on aging and stress resistance were shown to be dependent on enhanced fat metabolism but not due to its antioxidant effects, suggesting that vitamin K2 could enhance fat degradation and digestion to improve survival, supporting the effectiveness of vitamin K2-based medical treatments [214].…”

Maackiain Mimics Caloric Restriction through aak-2-Mediated Lipid Reduction in Caenorhabditis elegans

“…Over 4 million deaths per year are attributed to obesity-derived diseases [3][4][5][6][7]. The development of effective obesity therapy is an enormous challenge due to its complex etiology and pathophysiology [1,[5][6][7][8]. Moreover, the side effects of the long-term prescription of approved anti-obesity medicines, such as gastro-intestinal disturbances, as well as insufficient efficacy encourage the development of novel approaches for obesity management [2,9].…”