The lipid profile of brown adipose tissue is sex-specific in mice

Abstract

Brown adipose tissue (BAT) is a thermogenic organ with a vital function in small mammals and potential as metabolic drug target in humans. By using high-resolution LC-tandem-mass spectrometry, we quantified 329 lipid species from 17 (sub)classes and identified the fatty acid composition of all phospholipids from BAT and subcutaneous and gonadal white adipose tissue (WAT) from female and male mice. Phospholipids and free fatty acids were higher in BAT, while DAG and TAG levels were higher in WAT. A set of phospholipids dominated by the residue docosahexaenoic acid, which influences membrane fluidity, showed the highest specificity for BAT. We additionally detected major sex-specific differences between the BAT lipid profiles, while samples from the different WAT depots were comparatively similar. Female BAT contained less triacylglycerol and more phospholipids rich in arachidonic and stearic acid whereas another set of fatty acid residues that included linoleic and palmitic acid prevailed in males. These differences in phospholipid fatty acid composition could greatly affect mitochondrial membranes and other cellular organelles and thereby regulate the function of BAT in a sex-specific manner.

Oxidative Lipidomics Coming of Age: Advances in Analysis of Oxidized Phospholipids in Physiology and Pathology

“…In fact, the major problem with nontargeted MS analysis is the amount of data available, exemplified by the size of a typical data file for a 1 h LC-MSMS run of 0.5 GB, and the consequent complexity of its analysis. For example, recent lipidomic studies of LDL have identified between 150 and 275 native molecular lipid species (13, 100), a study of mouse plasma using SFC identified 461 lipids (145), many lipids have been comprehensively profiled in brown adipose tissues (47), and other reports have identified even higher numbers (11); the likely number of different oxidized forms is considerably higher than this, and many different oxidized phospholipids have been reported in diseased tissues. The manual identification of such large numbers of species becomes an impossible task, and other approaches are required to make the data manageable.…”

Development of a mass-spectrometry-based lipidomics platform for the profiling of phospholipids and sphingolipids in brain tissues

“…Given that most analysis methods focus only on one or a few specific lipid classes, lipid profiling needs to be extended so that additional important lipid classes can be covered. Targeted and nontargeted lipidomic profiling of hundreds of lipid species in various tissues and plasma are mainly accomplished by high-resolution accurate-mass MS, such as time-of-flight MS and Orbitrap MS [14,[24][25][26].…”

Form(ul)ation of adipocytes by lipids

“…9 Mitochondria in brown adipocytes are characterized by their own set of lipids, which include different types of PL and the 4-acyl chain cardiolipins. 24,27 The latter are abundant in mitochondrial lamellar crista architecture. Inner mitochondrial membranes of brown/beige adipocytes are marked by the expression of uncoupling protein-1 (UCP-1), which can disrupt the proton gradient generated in mitochondrial oxidative phosphorylation to generate heat.…”

“…26 PCA plots also show that BAT is distinct from closelyassociated clusters of SWAT and VWAT, and that BAT lipidomes additionally display sexual dimorphism between males and females. 27 Of note, BAT, as compared with WAT, consists of more saturated TG, 26 theoretically because saturated fatty acids (SFA) generate more ATP than polyunsaturated fatty acids (PUFA) as an efficient energy source. In addition, BAT consists of higher levels of cardiolipins and PL, 27 which reflect their relative abundancy in the mitochondria.…”

“…27 Of note, BAT, as compared with WAT, consists of more saturated TG, 26 theoretically because saturated fatty acids (SFA) generate more ATP than polyunsaturated fatty acids (PUFA) as an efficient energy source. In addition, BAT consists of higher levels of cardiolipins and PL, 27 which reflect their relative abundancy in the mitochondria. Mitochondria biogenesis is high in brown adipocytes and is increased following stimuli, such as cold exposure.…”