Glycerol-3-phosphate acyltransferases and metabolic syndrome: recent advances and future perspectives

Abstract

Triglycerol-3-phosphate acyltransferases (GPATs) are the key enzymes in the first step of the synthesis of triacylglycerol (TAG). In mammals, there are four isoforms of GPATs. GPAT1 and GPAT2 are localised in the outer mitochondrial membrane, while GPAT3 and GPAT4 are localised in the endoplasmic reticulum. Previous research has emphasised that GPAT plays a critical effect on the development of metabolic syndromes, such as liver steatosis, obesity, and insulin resistance. In this review, we will critically evaluate the regulatory effects of GPATs isoforms in metabolic syndrome. In addition, we also discuss perspectives on clinical intervention strategies for the neurometabolic disease.

Circadian organization of lipid landscape is perturbed in type 2 diabetic patients

“…This change may explain the phospholipid level alterations, along with the trend for higher PC/PE ratio upon T2D ( Figures 3 A, 3B, and S4 F). Similarly, RNA expression of AGPAT9 , the key enzyme in de novo synthesis of lysophosphatidic acid, 43 whose activity is enhanced by insulin stimulation, 44 , 45 was downregulated in the SAT of T2D subjects ( Figure S4 G). It is thus plausible to hypothesize that circadian regulation of the rhythmic lipid landscape might be mediated, at least in part, via the rhythmic regulation of the key enzymes of the lipid metabolism, like it has been previously reported for the circadian regulation of various metabolic pathways.…”

11β-HSD1 inhibitor efficacy in type 2 diabetes is cortisol-dependent

“…Further, we found that AZD4017 induced thromboprotective ADAMTS13, PROCR, STAB2, PLAU, and reduced prothrombotic SERPINE1, with differential expression of other coagulation genes (PROS1, PLAT, VWF, ST3GAL4, RUNX1) also suggesting a novel role for 11β-HSD1 in the regulation of haemostasis [33][34][35]. Other novel 11β-HSD1 targets include AZD4017-upregulated SOSTDC1; a TGF-beta inhibitor associated with endometrial receptivity [36], PIEZO2; a cation channel associated with mechanosensation and diabetic neuropathy [37,38], and key regulators of metabolism such as GPAT3 [39,40], STEAP4 [41], HMGCS2, and SOX4 [42].…”

Acyltransferases in the first step of glycerophospholipid synthesis have redundant and non-redundant roles insn-1 acyl chain regulation, ether lipid levels, and cell survival

“…Our study revealed the multifaceted functions of GPATs and GNPAT, in the regulation of ether lipids, acyl chains, and bulk lipid synthesis. Knockout mouse studies revealed the functions of these enzymes 12 , but the molecular mechanisms of lipid functions affected in these mice have been typically difficult to investigate. Our study contributes to a better understanding about the metabolic functions of these enzymes, and thus will help the establishment of hypotheses when investigate the knockout mice in the future.…”

“…Besides their localization, GPATs have differences in acyl-CoA preferences, at least when analyzed with in vitro assays 12 . Given the importance of proper GPL acyl chain compositions in cells, it is critical to know whether acyl-CoA preferences of GPATs and GNPAT affect lipid composition in cellular contexts.…”