Adipose tissue-derived lipokines in metabolism

Abstract

Adipose tissue is a crucial regulator of metabolism with functions that include energy storage and dissipation as well as the secretion of bioactive molecules. As the largest endocrine organ in the body, the adipose tissue produces diverse bioactive molecules, including peptides, metabolites, and extracellular vesicles, which communicate with and modulate the function of other organs. In recent years, lipid metabolites, also known as lipokines, have emerged as key signaling molecules that actively participate in multiple metabolic processes. This review highlights the latest advances in adipose tissue-derived lipokines and their underlying cellular and molecular functions. Furthermore, we offer our perspective on the future directions for adipose-derived bioactive lipids and potential therapeutic implications for obesity and its associated complications.

Figure 1.. Biosynthetic pathways for adipose tissue-derived lipokines.

A schematic representation of the biosynthetic pathway consisting of adipose tissue-derived lipokines, its precursor fatty acid, and sequential enzymes. Palmitoleate (16:1n-7) is synthesized from palmitic acid by the action of stearoyl-coenzyme A desaturase 1 (SCD1). 5-PAHSA and 9-PAHSA are FAHFAs in which palmitic acid are esterified to 5-hydroxy stearic acid and 9-hydroxy stearic acid, respectively. PGE2 and 12,13-diHOME are synthesized from ω-6 polyunsaturated fatty acids (PUFAs) arachidonic acid (AA) and linoleic acid (LA), respectively. 12-HEPE and MaR2 are endogenously synthesized as a downstream product of ω-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), respectively. ATGL: Adipose triglyceride lipase, COXs: Cyclooxygenases, CYP450: Cytochrome P450, FAHFAs: Fatty acid esters of hydroxy fatty acids, HSL: Hormone-sensitive lipase, LOX: Lipoxygenase, MaR1: Maresin-1, MaR2: Maresin-2, MGL: Monoglyceride lipase, mPGES: microsomal Prostaglandin E synthase, PAHSAs: Palmitic acid hydroxystearic acids, sEH: soluble epoxide hydrolase, TG: Triglycerides

Figure 2.. Inter-organ crosstalk mediated by adipose tissue-derived lipokines.

A schematic illustration depicts the role of adipose tissue-derived lipokines in regulating nutrient utilization, thermogenesis, and systemic metabolism by communicating with other metabolic organs. Lipokines from brown/beige (brite) adipose tissue (red font) and white adipose tissue (blue font) play diverse roles in inter-organ communication.