Naringenin Promotes Thermogenic Gene Expression in Human White Adipose Tissue

OBJECTIVE: Naringenin, a citrus flavonoid, prevents diet-induced weight gain and improves glucose and lipid metabolism in rodents. There is evidence that naringenin activates brown fat and increases energy expenditure in mice, but little is known about its effects in humans. Our goal was to examine the effects of naringenin on energy expenditure in adipose tissue. METHODS: Human white adipocyte cultures (hADSC), and subcutaneous abdominal adipose tissue (pWAT) were treated with naringenin for 7–14 days. Expression (qRT-PCR, immunoblotting) of candidate genes involved in thermogenesis and glucose metabolism was measured. Oxygen consumption rate (OCR) was measured in hADSC using a Seahorse Flux analyzer. RESULTS: In hADSC, naringenin increased expression of the genes associated with thermogenesis and fat oxidation including uncoupling protein 1, adipose triglyceride lipase, and key factors associated with insulin sensitivity including glucose transporter 4, adiponectin, and carbohydrate response element binding protein (p<0.01). Similar responses were observed in pWAT. Basal, ATP-linked, maximal, and reserve OCR increased in the naringenin-treated hADSC (p<0.01). CONCLUSIONS: Naringenin increases energy expenditure in hADSC and stimulates expression of key enzymes involved in thermogenesis and insulin sensitivity in hADSC and pWAT. Naringenin may promote conversion of human white adipose tissue to a brown/beige phenotype.