Perilipin 2 and Age-Related Metabolic Diseases: A New Perspective

Perilipin 2 (Plin2) is linked to lipid deposition in nonadipose tissues and its increased expression is associated with various metabolic diseases (insulin resistance, type 2 diabetes, atherosclerosis, and cardiovascular diseases) in both animals and humans, with the notable exception of endurance athletes. Downregulation of Plin2 in vivo protects animal models against experimentally induced metabolic diseases, suggesting a broader role for Plin2 beyond lipid storage. Plin2 expression appears to also be associated with pathological conditions such as sarcopenia and cancer, both age-related diseases. Experimental data suggest that, at least in non-alcoholic fatty liver disease, a possible link between Plin2 and liver steatosis could be inflammation. It is possible, but not yet demonstrated, that this link also exists for other pathologies that have been associated with increased Plin2 expression. Perilipin 2 (Plin2), a protein associated with the metabolism of intracellular lipid droplets (LDs), has long been considered only for its role in lipid storage. However, the manipulation of its expression affects the severity of a variety of metabolic and age-related diseases, such as fatty liver, insulin resistance and type 2 diabetes (T2D), cardiovascular disease, atherosclerosis, sarcopenia, and cancer, suggesting that this protein may play a role in these pathological conditions. In particular, its downregulation in mice prevents or mitigates some of the above mentioned diseases. Conversely, in humans high levels of Plin2 are present in sarcopenia, hepatic steatosis, atherosclerosis, and some types of cancer. We propose that inhibition of Plin2 might be a strategy to counteract several metabolic and age-related diseases. Perilipin 2 (Plin2), a protein associated with the metabolism of intracellular lipid droplets (LDs), has long been considered only for its role in lipid storage. However, the manipulation of its expression affects the severity of a variety of metabolic and age-related diseases, such as fatty liver, insulin resistance and type 2 diabetes (T2D), cardiovascular disease, atherosclerosis, sarcopenia, and cancer, suggesting that this protein may play a role in these pathological conditions. In particular, its downregulation in mice prevents or mitigates some of the above mentioned diseases. Conversely, in humans high levels of Plin2 are present in sarcopenia, hepatic steatosis, atherosclerosis, and some types of cancer. We propose that inhibition of Plin2 might be a strategy to counteract several metabolic and age-related diseases. the main alcohol-related pathological condition in Western countries. Excessive and chronic alcohol consumption is characterized by the accumulation of LDs in liver cells and induces the secretion of proinflammatory cytokines that cause inflammation and apoptosis in hepatocytes, with differing degrees of severity from steatosis to cirrhosis. lipids comprising a fatty acid and a sphingosine. Many different ceramides exist and are involved in several physiological and pathological cellular processes including differentiation, proliferation, cell senescence, and apoptosis. fatty acids that are present in unbound (unesterified) form, with a hydrocarbon chain of 4–28 carbons. They can be esterified with glycerol to yield mono-, di-, and triglycerides, which represent the main forms of stored lipid. a state of chronic, sterile, subclinical inflammation observed in the elderly as an age-associated increase in circulating proinflammatory compounds. multiprotein oligomer that promotes the maturation of inflammatory cytokines such as IL-1β and IL-18 and is involved in innate immune responses. The inflammasome is involved in the initiation or progression of many ‘autoinflammatory’ diseases but also in metabolic disorders and neurodegenerative diseases. a complex process in which the three main metabolic tissues–skeletal muscle, liver, and white adipose tissue–become resistant to insulin and consequently its downstream signaling on metabolic pathways is impaired. Prolonged insulin resistance leads to T2D. mechanism of toxicity mediated by an excess of lipid metabolites such as DGs or ceramides that promotes the infiltration and activation of macrophages within tissues causing chronic inflammation. pathological condition characterized by the accumulation of hepatocellular LDs in the absence of alcohol consumption or other causes of chronic liver disease that leads to deregulation of lipogenic pathways, impairment of mitochondrial fatty acid oxidation, and inhibition of TG secretion. the gradual and progressive loss of skeletal muscle mass and function characterizing old age. It is estimated that males experience a loss of about 1% skeletal muscle mass per year after the age of 40 [61Narici M.V. Maffulli N. Sarcopenia: characteristics, mechanisms and functional significance.Br. Med. Bull. 2010; 95: 139-159Crossref PubMed Scopus (480) Google Scholar].