Hokkaido University · Medicine
Professor Hideaki Miyoshi's research lab focuses on the molecular mechanisms regulating lipid metabolism in adipocytes, with a central emphasis on the role of perilipin A and its post-translational modifications in controlling lipolysis and lipid storage. The lab investigates how protein kinase A (PKA)-mediated phosphorylation of perilipin A orchestrates the recruitment and activation of key lipases such as ATGL and HSL, thereby modulating energy homeostasis. Using genetically engineered mouse models and primary adipocytes, the lab explores the physiological and pathological implications of perilipin dysregulation in obesity, insulin resistance, and autoimmune pancreatitis (AIP). Their work also extends to identifying novel therapeutic targets by manipulating lipid droplet-associated proteins to induce a metabolically beneficial brown-like phenotype in white adipose tissue.
Figures are computed from collected data and may differ slightly.
Hormone-sensitive lipase (HSL) is the predominant lipase effector of catecholamine-stimulated lipolysis in adipocytes. HSL-dependent lipolysis in response to catecholamines is mediated by protein kinase A (PKA)-dependent phosphorylation of perilipin A (Peri A), an essential lipid droplet (LD)-associated protein. It is believed that perilipin phosphorylation is essential for the translocation of HSL from the cytosol to the LD, a key event in stimulated lipolysis. Using adipocytes retrovirally eng
Phosphorylation of the lipid droplet-associated protein perilipin A (Peri A) mediates the actions of cyclic AMP-dependent protein kinase A (PKA) to stimulate triglyceride hydrolysis (lipolysis) in adipocytes. Studies addressing how Peri A PKA sites regulate adipocyte lipolysis have relied on non-adipocyte cell models, which express neither adipose triglyceride lipase (ATGL), the rate-limiting enzyme for triglyceride catabolism in mice, nor the "downstream" lipase, hormone-sensitive lipase (HSL).
Increased numbers of CD4+CD25high Tregs may influence IgG4 production in AIP, whereas decreased numbers of naïve Tregs may be involved in the pathogenesis of AIP.
In adipocytes, lipid droplet (LD) size reflects a balance of triglyceride synthesis (lipogenesis) and hydrolysis (lipolysis). Perilipin A (Peri A) is the most abundant phosphoprotein on the surface of adipocyte LDs and has a crucial role in lipid storage and lipolysis. Adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) are the major rate-determining enzymes for lipolysis in adipocytes. Each of these proteins (Peri A, ATGL, and HSL) has been demonstrated to regulate lipid stora
These findings demonstrate that overexpression of PeriA in white adipocytes reduces lipid droplet size by decreasing FSP27 expression and thereby inducing a brown adipose tissue-like phenotype. Our data suggest that modulation of lipid droplet proteins in white adipocytes is a potential therapeutic strategy for the treatment of obesity and its related disorders.
Perilipin A is the most abundant phosphoprotein on adipocyte lipid droplets and is essential for lipid storage and lipolysis. Perilipin null mice exhibit diminished adipose tissue, elevated basal lipolysis, reduced catecholamine-stimulated lipolysis, and increased insulin resistance. To understand the physiological consequences of increased perilipin expression in vivo, we generated transgenic mice that overexpressed either human or mouse perilipin using the adipocyte-specific aP2 promoter/enhan
Increased quantities of inducible costimulator-positive Tregs may influence IgG4 production in IgG4-related AIP.
UMIN Clinical Trials Registry System UMIN 000004955.
UMIN Clinical Trials Registry System as trial ID UMIN000005331.
Dapagliflozin might be more beneficial than pioglitazone in patients with NAFLD. Improvements in FLI would be closely related to glycemic control.
Weekly administration of dulaglutide was superior to liraglutide with regard to treatment satisfaction in patients with type 2 diabetes, in the absence of any negative effect on glycemic control.
Aminoguanidine inhibits the formation of advanced glycation end-products, and has been extensively examined in animals. However, administration of aminoguanidine decreases the hepatic content of pyridoxal phosphate. In order to avoid this problem, we developed an aminoguanidine pyridoxal Schiff base adduct and examined its efficacy in vitro as well as in a model of diabetic nephropathy. Mice with streptozotocin-induced diabetes were treated with aminoguanidine or aminoguanidine pyridoxal adduct
Once-weekly semaglutide administration improved glycaemic control and treatment satisfaction after switching from liraglutide or dulaglutide. These results highlighted a useful treatment option for patients with metabolic abnormalities despite glucagon-like receptor-1 receptor agonist treatment.
Open papers in the app to read, cite, and organize with AI.
