Fat storage-inducing transmembrane proteins: beyond mediating lipid droplet formation

Abstract

Fat storage-inducing transmembrane proteins (FITMs) were initially identified in 2007 as members of a conserved endoplasmic reticulum (ER) resident transmembrane protein gene family, and were found to be involved in lipid droplet (LD) formation. Recently, several studies have further demonstrated that the ability of FITMs to directly bind to triglyceride and diacylglycerol, and the diphosphatase activity of hydrolyzing fatty acyl-CoA, might enable FITMs to maintain the formation of lipid droplets, engage in lipid metabolism, and protect against cellular stress. Based on the distribution of FITMs in tissues and their important roles in lipid droplet biology and lipid metabolism, it was discovered that FITMs were closely related to muscle development, adipocyte differentiation, and energy metabolism. Accordingly, the abnormal expression of FITMs was not only associated with type 2 diabetes and lipodystrophy, but also with cardiac disease and several types of cancer. This study reviews the structure, distribution, expression regulation, and functionality of FITMs and their potential relationships with various metabolic diseases, hoping to provide inspiration for fruitful research directions and applications of FITM proteins. Moreover, this review will provide an important theoretical basis for the application of FITMs in the diagnosis and treatment of related diseases.

Challenges in Pharmacological Intervention in Perilipins (PLINs) to Modulate Lipid Droplet Dynamics in Obesity and Cancer

“…This stage requires the involvement of additional proteins that facilitate the expansion of the neutral lipid core and help stabilize the TAG aggregates [25]. The proteins involved in this process primarily consist of fat storage-inducing transmembrane proteins (FIT or FITM) and SEIPIN [26,27]. FIT proteins are localized to the ER, and both of their isoforms, FIT1 and FIT2, participate in LD biogenesis [26,27].…”

“…The proteins involved in this process primarily consist of fat storage-inducing transmembrane proteins (FIT or FITM) and SEIPIN [26,27]. FIT proteins are localized to the ER, and both of their isoforms, FIT1 and FIT2, participate in LD biogenesis [26,27]. Rather than synthesizing neutral lipids, FIT1 and FIT2 assist in integrating TAG into LDs [26,27].…”

“…FIT proteins are localized to the ER, and both of their isoforms, FIT1 and FIT2, participate in LD biogenesis [26,27]. Rather than synthesizing neutral lipids, FIT1 and FIT2 assist in integrating TAG into LDs [26,27]. When FIT proteins are overexpressed, they result in LDs enriched with TAG [26].…”