Aging and ß3-adrenergic stimulation alter mitochondrial lipidome of adipose tissue.

Mitochondrial abundance and thermogenic capacity are two imperative components that distinguish brown, beige and white adipose tissues. Most importantly, the lipid composition is vital for maintaining the quantity, quality and function of mitochondria. Therefore, we employed quantitative lipidomics to probe the mitochondrial lipidome of adipose tissues. The mitochondrial lipidome reveals ß3-adrenergic stimulation and aging drastically altered the levels of phosphatidylcholine (PC)/phosphatidylethanolamine (PE) ratio and acyl chain desaturation. Precisely, PC36:2 and PE38:4 levels correlate with the increased brown and beige fat activity in young mice. While aging increased lysoPC species in white adipose tissue (WAT) mitochondria, CL-316,243 administration reduced lysoPC species and increased lyso-PE18:1 and 18:2 content during WAT browning. Also, non-thermogenic mitochondria accumulate sphingomyelin (SM), phosphatidylserine (PS), phosphatidic acid (PA) and ether-linked PC (ePC). Similarly, enrichment of phosphatidylglycerol (PG) and cardiolipin (CL) levels are associated with thermogenic mitochondria. Also, our in vitro experiment supports that blocking the de novo sphingolipid synthesis pathway by myriocin, SPT1 inhibitor increased the thermogenic capacity and oxygen consumption rate in mature adipocytes. Overall, our study suggests mitochondria of brown, beige and white adipose tissues own a unique pattern of lipid molecular species and their levels are altered by aging and CL-316,243 administration.

Sesaminol induces brown and beige adipocyte formation through suppression of myogenic program.

Adipocytes are key players in maintaining energy homeostasis and are classified into two different categories: white and brown adipocytes. While white adipocytes store energy as triacylglycerols in lipid droplets, brown adipocytes combust excess chemical energy and release in the form of heat through uncoupled respiration. This characteristic phenomenon of brown fat attracts researchers and pharmacological industries to view brown fat as one of the potential therapeutic targets for obesity and associated metabolic disease. In the current study, we investigated the effect of a small molecule, sesaminol (SML) on brown fat activity and found that SML induces the thermogenic program in primary white adipocytes as well as chow diet fed mice. In particular, SML treatment to mice elevated mitochondrial complex proteins and the rate of oxygen consumption in brown and white fat. Administration of SML to high fat diet (HFD) challenged mice decreased weight gain, adiposity and cholesterol levels along with an increase of brown fat gene program in brown and white fat. Mechanistically, SML repressed the myogenic gene program in C2C12 myoblasts and increased all mitochondrial marker genes as appeared in brown adipose cells. Together, our results demonstrate that SML stimulates brown adipose function and protects mice against diet-induced weight gain.