Adipocytes hold the main source of energy stored in the body in the form of triacylglycerols (TAG). It is known that the hydrolysis of TAGs and the release of nonesterified free fatty acids and the resulting glycerol can be regulated by a process which depends on a lipolysis reaction messenger molecule, cyclic adenosine monophosphate (cAMP).
The increased concentration of cAMP in adipocytes activates kinase A which, by phosphorylation, activates HSL which then breaks down triglycerides into free fatty acids and glycerol. The glycerol is then transported out of the cell. After the first signalling cascade, the details of this lipolytic reaction have remained unclear up until now. Research over the last few years has revealed that HSL and perilipin, a lipid droplet surface protein, are needed to optimise lipid storage and release of fatty acids.1 Lipid droplets are coated with one or more of five proteins that are members of the perilipin family: adipophilin (ADRP), tail-interacting protein of 47 kDa (TIP47), oxidative tissues-enriched PAT protein (OXPAT), also called myocardial lipid droplet protein or MLDP, S3-12, and perilipin A. The nature of the proteins covering lipid droplets changes during their biogenesis. Therefore, access to HSL is limited by the presence of proteins around the lipid droplets, particularly perilipin A.2 This protein acts like a protective layer against lipases such as HSL.3 Under basal conditions, perilipin A restricts cytosolic lipase access to lipid droplets and thus promotes triacylglycerol storage. During periods of energy deficit, perilipin A is phosphorylated by PKA and promotes lipolysis to the maximum.4 Once it has been phosphorylated, perilipin A changes conformation and exposes the stored lipids to lipolysis mediated by HSL.
Perilipin A and adipophilin: targets to access large lipid droplets
Perilipin A and adipophilin act in a complementary way during the process of fat storage. Differentiation of preadipocytes, which up until that point are not capable of storing fat, in the young adipocyte is the first step in the fat storage process. Fats are taken in charge by adipophilin and stored as small lipid droplets. The development of young adipocytes into mature adipocytes is accompanied by a fall in the level of adipophilin and an increase in the level of perilipin A. Perilipin A takes in charge the fats, which are stored in the form of a single large lipid droplet. In addition to the take-on of fats, perilipin A protects large lipid droplets, by distributing itself over the droplet surface. The conventional lipolytic active agents generally act on small-sized adipocytes; therefore the current issue is to find an active compound which acts on large lipid droplets which contain far higher levels of triglycerides (TG). It can therefore be imagined that if perilipin A expression is reduced, lipase access to large lipid droplets will be promoted which will enable lysis of more triglycerides and would increase the effectiveness of our active ingredients. Codif International’s laboratories has been working on pinpointing and expression of perilipins as a function of various parameters: the level of adipocyte differentiation, the location and size of lipid droplets. They then analysed the effect of a pure oil of pink berries (Pink PepperSlim – INCI: Schinus Terebinthifolius Seed Extract) on these parameters.
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