Piecing together the puzzle of perilipin proteins and skeletal muscle lipolysis

Abstract

The regulation of skeletal muscle lipolysis and fat oxidation is a complex process involving multiple proteins and enzymes. Emerging work indicates that skeletal muscle PLIN proteins likely play a role in the hydrolysis of triglycerides stored in lipid droplets and the passage of fatty acids to the mitochondria for oxidation. In adipocytes, PLIN1 regulates lipolysis by interacting with comparative gene identification-58 (CGI-58), an activator of adipose triglyceride lipase (ATGL). Upon lipolytic stimulation, PLIN1 is phosphorylated, releasing CGI-58 to activate ATGL and initiate triglyceride breakdown. The absence of PLIN1 in skeletal muscle leads us to believe that other PLIN family members undertake this role. The focus of this review is on the PLIN family proteins expressed in skeletal muscle: PLIN2, PLIN3, and PLIN5. To date, most studies involving these PLIN proteins have used nonmuscle tissues and cell cultures to determine their potential roles. Results from work in these models support a role for PLIN proteins in sequestering lipases during basal conditions and in potentially working together for lipase translocation and activity during lipolysis. In skeletal muscle, PLIN2 tends to mirror the lipid content and may play a role in lipid droplet growth and stability through lipase interactions on the lipid droplet surface, whereas the skeletal muscle roles of both PLIN3 and PLIN5 seem to be more complex because they are found not only on the lipid droplet, but also at the mitochondria. Clearly, further work is needed to fully understand the intricate mechanisms by which PLIN proteins contribute to skeletal muscle lipid metabolism.

Reduced mitochondrial lipid oxidation leads to fat accumulation in myosteatosis

“…There was a down-regulation in nearly all of the genes responsible for the transport of FFAs into the muscle cells, and the synthesis of TGs from FFAs (53), including CD36, ACSL1, ACSL6, AGPAT9/glycerol-3-phosphate acyltransferase 3, glycerol-3-phosphate acyltransferase 1, mitochondrial, AGPAT1, AGPAT3, AGPAT6, lipin 1-3, and DGAT1-2. PLIN2, which coats lipid droplets and appears to be important for lipid droplet growth and stability (54), was also up-regulated after rotator cuff tear, whereas PLIN5, which also coats lipid droplets but also helps to target fatty acids to mitochondria for oxidation (54), was down-regulated. Consistent with these findings, genes involved with hydrolyzing TG stored in lipid droplets in fatty acids (53,55) were down-regulated after injury, including ATGL and PNPLA3, hormone-sensitive lipase, and monoglyceride lipase.…”

Reduced mitochondrial lipid oxidation leads to fat accumulation in myosteatosis

“…FFAs (48), including CD36, ACSL1, ACSL6, AGPAT9/GPAT3, GPAM, AGPAT1, AGPAT3, AGPAT6, lipin 1-3, and DGAT1-2. Perilipin 2, which coats lipid droplets and appears to be important for lipid droplet growth and stability (49) was also upregulated after rotator cuff tear, while perilipin 5 which also coats lipid droplets but also helps to target fatty acids to mitochondria for oxidation (49), was downregulated. Consistent with these findings, genes involved with hydrolyzing triglyceride stored in lipid droplets into fatty acids (48,50) were downregulated after injury, including ATGL and PNPLA3, hormone sensitive lipase, and monoglyceride lipase.…”

Effect of Divergent Selection for Intramuscular Fat Content on Muscle Lipid Metabolism in Chickens

“…Each PLIN family member likely performs a unique function in the regulation of lipid droplet dynamics [35], and PLIN1 plays a "switch" role in regulating lipolysis. Native PLIN1 may serve as a barrier, protecting droplet triglycerides from basal lipolysis, whereas phosphorylated PLIN1 could indirectly activate ATGL [36,37]. Previous studies have found that the expression of PLIN1 was higher in muscles with high IMF contents [34,38].…”