Comprehensive and quantitative analysis of white and brown adipose tissue by shotgun lipidomics

Abstract

Shotgun lipidomics enables an extensive analysis of lipids from tissues and fluids. Each specimen requires appropriate extraction and processing procedures to ensure good coverage and reproducible quantification of the lipidome. Adipose tissue (AT) has become a research focus with regard to its involvement in obesity-related pathologies.However, the quantification of the AT lipidome is particularly challenging due to the predominance of triacylglycerides, which elicit high ion suppression of the remaining lipid classes. We present a new and validated method for shotgun lipidomics of AT, which tailors the lipid extraction procedure to the target specimen and features high reproducibility with a linear dynamic range of at least 4 orders of magnitude for all lipid classes. Utilizing this method, we observed tissue-specific and diet-related differences in three AT types (brown, gonadal, inguinal subcutaneous) from lean and obese mice.Brown AT exhibited a distinct lipidomic profile with the greatest lipid class diversity and responded to high-fat diet by altering its lipid composition, which shifted towards that of white AT. Moreover, diet-induced obesity promoted an overall remodelling of the lipidome, where all three AT types featured a significant increase in longer and more unsaturated triacylglyceride and phospholipid species.The here presented method facilitates reproducible systematic lipidomic profiling of AT and could be integrated with further -omics approaches used in (pre-)clinical research, in order to advance the understanding of the molecular metabolic dynamics involved in the pathogenesis of obesity-associated disorders.

AdipoAtlas: A reference lipidome for human white adipose tissue

“…Previously, obesity-driven global accumulation of longchain PUFA-containing TGs was demonstrated in murine models and human biopsies. [35][36][37][38] Increased activity of the FA elongase Elovl6 was proposed to play a role as a common phenomenon in rodent and human adipose tissue in response to excessive nutrient consumption. 38 This suggests that besides upregulation of total enzymatic FA elongation/desaturation machinery, the generation of specific TG molecular species is regulated during obesity development and opens up the questions of how and why specific lipogenic enzymes generate distinct TG species and what their role is in obesity development.…”

Changes in brown adipose tissue lipid mediator signatures with aging, obesity, and DHA supplementation in female mice

“…With this regard, a lipidomic study has revealed a dramatic switch in BAT lipidome toward a WAT‐like lipidome after a high‐fat feeding period of 20 weeks 28 . Regarding SPMs, a recent study has described Lipoxin A4 (LXA 4 ) and SPMs precursors 18‐HEPE, 17‐HDHA, and 15‐HETE among the main contributors to differentiate BAT from WAT fatty acid metabolomic phenotype 29 .…”