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

Abstract

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.