high-fat diet

Cetilistat (ATL-962) is a novel inhibitor of pancreatic lipase being developed by Alizyme for the treatment of obesity and associated co-morbidities, including type 2 diabetes.

Punicalagin is a major ellagitannin found in pomegranates that is reported to produce antioxidant, anti-inflammatory, and anticancer effects. It has been shown to prevent high-fat diet-induced obesity-associated accumulation of cardiac triglyceride and ch

Nicotinamide riboside increases NAD[+] levels and activates SIRT1 and SIRT3, culminating in enhanced oxidative metabolism and protection against high fat diet-induced metabolic abnormalities.

Rhododendrol (Frambinol) is a melanin synthesis and acts by preventing high-fat diet-induced elevation in body weight and increasing lipolysis in white adipocytes in male mice. Rhododendrol can be used as the lightening/whitening cosmetics inhibitor.

Oxfenicine (4-Hydroxy-L-phenylglycine) is a carnitine palmitoyltransferase-1 inhibitor. Oxfenicine improves whole-body glucose tolerance and insulin sensitivity in high-fat diet-induced obese mouse with insulin resistance.

SR 1903 is an inverse agonist of RORγ and PPARγ (IC₅₀ = 100 nM and 209 nM, respectively) and an agonist of LXR (EC₅₀ = 154 nM). It exerts anti-inflammatory and anti-diabetic effects in mouse models of collagen-induced arthritis and diet-induced obesity.

10,12-Tricosadiynoic acid is a highly selective and orally active inhibitor of acyl-CoA oxidase-1 (ACOX1), which can treat high-fat diet- or obesity-induced metabolic diseases by improving mitochondrial lipid and ROS metabolism.

Bixin is an orally active carotenoid that modulates TLR4/NF-κB, Nrf2, and ROS to mitigate high-fat diet-induced cardiac injury in mice and induces apoptosis in A549, HeLa, and MCF-7 cells.

KPLH1130, a specific pyruvate dehydrogenase kinase (PDK) inhibitor, enhances glucose tolerance in mice fed a high-fat diet (HFD). It effectively hinders macrophage polarization and mitigates proinflammatory reactions.

PCSK9-IN-29 serves as a lipid-lowering agent that enhances the expression of low-density lipoprotein receptor (LDLR) protein and reduces PCSK9 protein expression in hepG2 cells. Additionally, in crab-eating macaques on a high-fat diet, it lowers serum LDL-C, TC, and liver enzyme ALT levels, reduces body weight and fat, and boosts bone mineral content. PCSK9-IN-29 is useful for studies involving non-alcoholic fatty liver disease and obesity.

ALG-055009, a thyroid hormone receptor β (THR-β) agonist, exhibits an EC50 of 0.063 μM. It has been shown to reduce total cholesterol levels in rats fed a high-fat diet. ALG-055009 is used in the study of fatty liver diseases associated with metabolic dysfunction.

HPG1860, an agonist of the farnesoid X receptor (FXR), induces luminescence in reporter gene assays utilizing HEK293T cells expressing human FXR, with an EC50 value of 18 nM. In vivo studies demonstrate that HPG1860 (administered at 1, 3, or 10 mg/kg daily) reduces serum alanine aminotransferase (ALT) and total cholesterol levels in a mouse model of non-alcoholic steatohepatitis (NASH), which was induced by a high-fat diet and carbon tetrachloride (CCl4). Additionally, this compound decreases hepatic inflammation, fat levels, and fibrosis.

E17241 functions as an inducer of ABCA1 gene expression, effectively increasing its expression with an EC50 value of 280 nM. It also acts as an agonist for peroxisome proliferator-activated receptors (PPARs), inducing PPAR-mediated gene expression in HepG2 cells expressing PPARγ, PPARα, or PPARδ, with respective EC50 values of 290, 3,900, and 879 nM. In RAW 264.7 macrophage cells, E17241 enhances ACBA1 protein levels, although this effect is absent when siRNA targeting PKCζ mRNA is present. Treatment with E17241 (0.4, 2, or 10 µM) increases cholesterol efflux in RAW 264.7 cells. In an atherosclerosis model using ApoE-/- mice administered with a dose of 25 mg/kg, E17241 reduces levels of plasma cholesterol, alanine transaminase (ALT), aspartate transaminase (AST), and liver cholesterol and triglycerides, and also decreases the area of aortic lesions. Additionally, daily administration of E17241 (50 mg/kg) lowers blood glucose levels and body weight in KKAy diabetic mice on a high-fat, high-glucose (HFHG) diet.

D-Psicose (D-Allulose) is an orally active rare sugar. It effectively inhibits p38-MAPK phosphorylation and MCP-1 expression, while blocking the AGEs/RAGE/NF-kappaB signaling pathway. D-Psicose demonstrates significant bioactivity in research involving pancreatic beta-islet protection, hyperglycemia improvement, lipid metabolism regulation, and the mitigation of high-fat diet-induced non-alcoholic fatty liver disease (NAFLD).

Wnt/β-catenin activator 1 (Compound 5m) is an orally active activator of the Wnt/β-catenin signaling pathway. It induces cell cycle arrest in the G1 phase, inhibits early proliferation of adipocytes, and suppresses adipogenesis in 3T3-L1 cells with an IC50 of 330 nM. In a high-fat diet-fed Syrian golden hamster model, Wnt/β-catenin activator 1 exhibits anti-adipogenic and anti-dyslipidemic activities.

Urobilinogens comprise a mixture of bilirubin metabolites, including D-urobilinogen, L-urobilinogen (stercobilinogen), and i-urobilinogen (mesobilirubinogen). These compounds are produced from bilirubin by gut microbiota. In mice on a high-fat diet, the cecal concentrations of D-urobilinogen, L-urobilinogen, and i-urobilinogen are increased. Furthermore, elevated fecal levels of L-urobilinogen are inversely associated with reduced blood hemoglobin levels in patients with heterozygous β-thalassemia.

LCZ960 is an orally active glucokinase (GK) activator that stimulates GK activity in liver cells in vitro and enhances glucose uptake in vivo by activating hepatic GK. It effectively lowers blood glucose levels in diet-induced obesity (DIO) in mice. LCZ960 maintains normal blood sugar and improves glucose tolerance in DIO mice and rats. Additionally, LCZ960 stimulates glycogen synthase flux and increases glycogen turnover in the liver of rats, inducing an increase in hepatic glycogen cycling. This compound is useful for research on obesity and type 2 diabetes induced by high-fat diets.

GPR109 receptor agonist-3 is an orally active GPR109 receptor agonist with an IC50 of 310 nM. It retains the antioxidant and cytoprotective properties of lipoic acid. In rats on a high-fat diet, GPR109 receptor agonist-3 reduces total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C), while increasing high-density lipoprotein cholesterol (HDL-C). This compound is applicable for atherosclerosis research.

THR-β agonist 11 is an orally active and selective thyroid hormone receptor (THR-β) agonist. It demonstrates robust cholesterol-lowering effects in cholesterol-fed rats. In a high-fat diet-carbon tetrachloride (HFD-CCl4) induced model of metabolic dysfunction-associated steatohepatitis (MASH) in mice, THR-β agonist 11 significantly reduces serum total triglycerides (TG), low-density lipoprotein cholesterol (LDL-cholesterol), liver total cholesterol (TC), and TG levels. Additionally, it alleviates hepatic steatosis, inflammation, and fibrosis. THR-β agonist 11 is applicable in the study of MASH and other fibrotic diseases.

VSP-77 is an orally active PPARγ agonist. It selectively enhances the expression of insulin sensitivity-related genes (Glut4 and Adiponectin) by inhibiting CDK5-mediated phosphorylation of PPARγ at Ser-273. In a high-fat diet-induced diabetic mouse model, VSP-77 significantly improves glucose tolerance and reduces fasting blood glucose and insulin levels. VSP-77 is applicable for diabetes research.

FXR agonist14 (Compound V15) is a partial, selective, orally active FXR agonist with an EC50 of 0.67 nM. It can ameliorate the pathological features in mice with MASH induced by a high-fat, high-sugar diet, and shows significant effects against cholestatic liver disease.

SSTR5 antagonist4 (compound 1) is a potent, highly selective, and orally bioavailable antagonist of somatostatin subtype 5 (SSTR5) with an hSSTR5 IC50 of 1.3 nM and an mSSTR5 IC50 of 1.0 nM. It has demonstrated effectiveness in oral glucose tolerance tests (OGTT) in high-fat diet (HFD) mice and is applicable in research related to type 2 diabetes.

Oltipraz metabolite M2 is the active metabolite of Oltipraz and acts as an orally effective HIF-1α inhibitor. In a high-fat diet mouse model, it enhances mitochondrial fuel oxidation and suppresses hepatic lipogenesis by dual activation of AMPK. Oltipraz metabolite M2 is applicable for research in hepatic steatosis and fatty liver disease.

p-nitro-Pifithrin-α is a cell-permeable analog of pifithrin-α, a potent p53 inhibitor. It suppresses p53-mediated TGF-β1 expression in HK-2 cells and inhibits the activation of caspase-3 by Zika virus (ZIKV) strains. Moreover, p-nitro-Pifithrin-α attenuates steatosis and liver injury in mice subjected to a high-fat diet, mitigating the effects of non-alcoholic fatty liver disease [1] [2] [3] [4].