The Mevalonate Pathway Is Indispensable for Adipocyte Survival

Abstract

SummaryThe mevalonate pathway is essential for the synthesis of isoprenoids and cholesterol. Adipose tissue is known as a major site for cholesterol storage; however, the role of the local mevalonate pathway and its synthesized isoprenoids remains unclear. In this study, adipose-specific mevalonate pathway-disrupted (aKO) mice were generated through knockout of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase (HMGCR). aKO mice showed serious lipodystrophy accompanied with glucose and lipid metabolic disorders and hepatomegaly. These metabolic variations in aKO mice were dramatically reversed after fat transplantation. In addition, HMGCR-disrupted adipocytes exhibited loss of lipid accumulation and an increase of cell death, which were ameliorated by the supplementation of mevalonate and geranylgeranyl pyrophosphate but not farnesyl pyrophosphate and squalene. Finally, we found that apoptosis may be involved in adipocyte death induced by HMGCR down-regulation. Our findings indicate that the mevalonate pathway is essential for adipocytes and further suggest that this pathway is an important regulator of adipocyte turnover.

Codium fragile Ameliorates High-Fat Diet-Induced Metabolism by Modulating the Gut Microbiota in Mice

“…Among them, some have been previously reported as obesity biomarkers. For example, mevalonate is involved in cholesterol synthesis and is essential for adipocyte survival, and isoprene biosynthesis has also been reported as a potential obesity marker [33,34]. Moreover, decreases in pyruvate fermentation and glycolysis may indicate the decrease in energy harvesting.…”

<p>Comparative Analysis of the Preventive Effects of Canagliflozin, a Sodium-Glucose Co-Transporter-2 Inhibitor, on Body Weight Gain Between Oral Gavage and Dietary Administration by Focusing on Fatty Acid Metabolism</p>

“…After 8 weeks of canagliflozin administration, body composition was measured using a body composition analyzer, the EchoMRI 3-in-1 system (Hitachi, Tokyo, Japan). 10…”

“…The adipose tissue and liver sections were stained with hematoxylin/eosin and Oil Red O/hematoxylin, respectively. 10…”

An extended reconstruction of human gut microbiota metabolism for personalized nutrition

“…Regarding the obese children´s samples, two relevant metabolites caught our attention, namely, isoprene and myricetin. The former is predicted to be produced exclusively in the obese condition and, interestingly, it has been reported to be involved in many metabolic disorders and as a potential obesity marker exhaled in breath 28,29 . With respect to myricetin, however, just the opposite occurs since it is only produced in the fermentations with inocula from the lean children´s stools but not in those from the obese children.…”