Selective activation of PPARα maintains thermogenic capacity of beige adipocytes.

Beige adipocytes are inducible thermogenic adipocytes used for anti-obesity treatment. Beige adipocytes rapidly lose their thermogenic capacity once external cues are removed. However, long-term administration of stimulants, such as PPARγ and ß-adrenergic receptor agonists, is unsuitable due to various side effects. Here, we reported that PPARα pharmacological activation was the preferred target for maintaining induced beige adipocytes. Pemafibrate used in clinical practice for dyslipidemia was developed as a selective PPARα modulator (SPPARMα). Pemafibrate administration regulated the thermogenic capacity of induced beige adipocytes, repressed body weight gain, and ameliorated impaired glucose tolerance in diet-induced obese mouse models. The transcriptome analysis revealed that the E-twenty-six transcription factor ELK1 acted as a cofactor of PPARα. ELK1 was mobilized to the Ucp1 transcription regulatory region with PPARα and modulated its expression by pemafibrate. These results suggest that selective activation of PPARα by pemafibrate is advantageous to maintain the function of beige adipocytes.

Variation in plasma glucagon levels according to obesity status in Japanese Americans with normal glucose tolerance.

Japanese Americans living in the United States are genetically identical to Japanese people, but have undergone a rapid and intense westernization of their lifestyle. This study investigated variability in glucagon secretion after glucose loading among Japanese Americans with normal glucose tolerance (NGT) according to obesity status. The 75-g oral glucose tolerance test (OGTT) was performed for 138 Japanese Americans (aged 40-75 years) living in Los Angeles. Plasma glucagon levels measured using the sandwich enzyme-linked immunosorbent assay were compared according to body mass index (BMI) categories among 119 individuals with NGT. The individuals were classified into three categories according to their BMI values: <22 kg/m2 (n = 37), 22-24.9 kg/m2 (n = 46), and ≥25 kg/m2 (n = 36). Fasting plasma glucagon levels and glucagon-area under the curve levels during the OGTT were the highest in the BMI ≥25 kg/m2 group. Fasting glucagon levels were correlated with BMI (r = 0.399, p < 0.001), fasting insulin levels (r = 0.275, p = 0.003) and the homeostasis model assessment-insulin resistance (r = 0.262, p = 0.004). In conclusion, our findings suggest that fasting hyperglucagonemia is associated with obesity and insulin resistance even during the NGT stage in the Japanese American population.