9-PAHSA

9-PAHSA is an orally effective endogenous GPR120 agonist (E_C50=18 μM). 9-PAHSA significantly inhibits LPS-induced inflammatory responses by blocking the NF-κB pathway. 9-PAHSA induces adipocyte browning, enhances glucose uptake and reduces lipid accumulation, while improving mitochondrial function and the survival rate of steatotic hepatocytes. In terms of neuroprotection, 9-PAHSA regulates the expression of REST and BDNF in the prefrontal cortex of diabetic mice, and effectively prevents spatial working memory deficits and abnormal social behaviors. 9-PAHSA does not directly regulate insulin secretion or improve systemic insulin sensitivity, and possesses specific anti-inflammatory, metabolic regulatory and neuroprotective properties. 9-PAHSA can be used in the research of diabetes-related cognitive impairment, obesity and non-alcoholic fatty liver disease^[1][2][3][4]. In Vitro:(R)-9-PAHSA and (S)-9-PAHSA (20 μM; 30 min pre-incubation) do not significantly increase basal or insulin-stimulated glucose uptake in human in vitro differentiated adipocytes^[1].
Racemic 9-PAHSA (1-20 μM; 2 h) does not stimulate glucose-dependent insulin secretion in dispersed mouse pancreatic islets^[1].
9-PAHSA (5-30 μM; 72 h) exhibits no significant cytotoxicity toward 3T3-L1 pre-adipocytes following 72 h of treatment^[3].
9-PAHSA (5-10 μM; 6 h) increases the viability of HepG2 cells with steatosis, with up to 140% relative viability observed in 500 μM oleic acid-treated cells, while higher 9-PAHSA concentrations reduce viability^[4].
9-PAHSA (10-40 μM; 6 h) reduces intracellular lipid accumulation in oleic acid-induced steatotic HepG2 cells^[4]. In Vivo:9-PAHSA (22.5 mg/kg; oral gavage; single acute dose) does not improve glucose tolerance or stimulate insulin or GLP-1 secretion in male C57BL/6J mice fed VS-LFD or VS-HFD for 18 weeks^[1].
9-PAHSA (45 mg/kg; oral gavage; single acute dose) does not improve glucose tolerance or stimulate insulin or GLP-1 secretion in male C57BL/6J mice fed BT-HFD for 18 weeks^[1].
9-PAHSA (15 mg/kg; oral gavage; single acute dose) does not improve glucose tolerance or stimulate glucose-stimulated insulin secretion in male C57BL/6J mice fed LARD-HFD for 20 weeks^[1].
9-PAHSA (50 mg/kg; i.g.; daily; 28 days) improves type 2 diabetes-associated cognitive impairment in db/db mice by reducing cortical REST expression and upregulating cortical BDNF expression, while also restoring spatial working memory and social novelty preference^[2].
9-PAHSA (50 mg/kg; p.o.; once daily; 28 days) promotes browning of subcutaneous inguinal white adipose tissue in both wild-type and ob/ob mice via upregulation of brown fat-specific genes and proteins, with more pronounced effects in ob/ob mice^[3].