Obesity-related osteopontin protein and methylation blood levels are differentially modulated by a very low-calorie ketogenic diet or bariatric surgery

BACKGROUND & AIM: Osteopontin (OPN) was proposed to play a role in the pathophysiology of obesity and related disease, such as cancer. The aims were to evaluate the expression of OPN after caloric restriction-induced weight loss in adipose tissue (AT) from an animal model of diet-induced obesity (DIO) and to reflect these results on circulating OPN levels in patients with obesity (PWO); and to explore the effect of a very low-calorie ketogenic diet (VLCKD) on the circulating protein and DNA methylation levels of OPN, compared with a balanced hypocaloric diet (LCD) or bariatric surgery (BS) in PWO. METHODS: OPN/SPP1 expression was evaluated in subcutaneous (SAT) and visceral (VAT) AT derived from diet-induced obesity (DIO) mice and after a 4-week weight-loss protocol of calorie restriction (CR). Plasmatic OPN was also evaluated in 32 normal-weight volunteers (20 women) and 79 PWO (59 women) and after a 4-6 months follow up of a VLCKD (n = 20), BS (n = 39) or LCD (n = 20). DNA methylation levels of OPN were extracted from our Infinium HumanMethylation450 BeadChips data sets. RESULTS: OPN levels were higher in VAT of DIO mice and plasma of PWO than in normal-weight individuals and changed after weight loss. Particularly, circulating OPN increased 2 months after BS while it decreased at maximum ketosis-induced by VLCKD. A statistically significant decrease was also observed in methylation levels at cg11226901 after VLCKD. CONCLUSIONS: OPN levels were reduced after VLCKD and severely increased after BS. Therefore, it could be a biomarker of the obesity-related metabolic stress and could be epigenetically regulated.