Perilipin 1 (PLIN1) is described as the major protein surrounding lipid droplets in adipocytes and steroidogenic cells where it regulates lipid storage and breakdown by controlling the interaction between lipases and triacylglycerol stores.

The PLIN1 protein is suggested to influence obesity risk and insulin resistance through its control of adipocyte metabolism, lipolysis and body fat accumulation. PLIN1 inhibits lipolysis in the fed state and promotes triacylglycerol storage by limiting lipase access to these fat stores. It however also participates in catecholamine-stimulated lipolysis through an interaction with lipid droplet-associated hormone-sensitive lipases in the fasted state. When perilipin 1 is phosphorylated by protein kinase A, it allows, and even recruits, enzymes to access lipid droplets to stimulate active lipolysis. The PLIN polymorphisms are reported to affect the perilipin protein content and thus the lipolytic rates of adipocytes, so modifying obesity risk in various populations. In animal studies, subjects lacking perilipin were observed as lean, resistant to diet-induced or genetic obesity and presented with peripheral insulin resistance.

The PLIN1 gene is located on the long arm of chromosome 15 (15q26). Of the seven SNPs identified in this gene, the 11482 G>A polymorphism is present in intron 6. This polymorphism has been associated with a decreased perilipin content and with increased basal and noradrenaline-induced lipolysis.    

A study of 148 Japanese male participants found that AA homozygotes had a significantly higher BMI, weight and waist circumference than G-allele carriers. This agrees with studies in Malays and Asian Indians but is contradictory to findings where the A-allele is associated with reduced obesity risk in women of the general Spanish population, possibly due to nutrigenetic effects.

Carbohydrate and Saturated Fat Intake 

Dietary factors seem to interact with the PLIN 11482 G>A polymorphism in modulating obesity risk. A higher intake of complex carbohydrates was found to be protective against obesity for A-allele carriers in a prospective cohort study of Caribbean-origin Hispanics. Similarly, a study involving a large multi-ethnic Asian population found that a lower carbohydrate intake was associated with adverse metabolic consequences in minor A-allele carriers and that carbohydrates were protective against insulin resistance. This protective effect against insulin resistance was supported by findings from a later study by Smith et al. (2012) where a lower carbohydrate and higher saturated fat intake was associated with higher insulin and HOMA-IR values.

Smith et al. (2008) investigated whether dietary macronutrients could influence the effect of the G>A SNP on obesity risk in a Puerto Rican population (Caribbean-origin Hispanics) comprised of 920 participants. Obesity measures such as waist and hip circumference and BMI did not differ between carriers and non-carriers, although a significant interaction was found between complex carbohydrate intake and waist and hip circumferences. In participants with a higher complex carbohydrate intake (≥ 144 g per day), the A-allele protected against obesity whereas with a lower complex carbohydrate intake (< 144 g per day), the A-allele was associated with increased obesity. No interaction was found for total carbohydrate or simple sugar intake.

A later study from Smith et al. (2012) investigated the association between the G>A SNP and insulin resistance and potential interactions with saturated fat and carbohydrate intake in a White population living in the United States (US). In female A-allele carriers only, it was reported that insulin and HOMA-IR (homeostasis model assessment of insulin resistance) was significantly higher with a low carbohydrate intake (< 50.5% of total energy), high saturated fat intake (≥ 11.5% of total energy) and high ratio of saturated fat to carbohydrate intake (≥ 0.23). Depicting this ratio as a continuous variable, it was found that as the ratio of saturated fat to carbohydrate intake increased, predicted HOMA-IR increased significantly for A-allele carriers but not for non-carriers.