Sex Differences in the Indole-3-propionic Acid Responses to Laparoscopic Roux-en-Y gastric Bypass

Abstract BACKGROUND Increased levels of indole-3-propionic acid (IPA), a gut-derived metabolite that lowers the risk of type 2 diabetes (T2D), may contribute to the metabolic benefits occurring after obesity surgery. We investigate whether the associations of serum IPA with insulin and glucose metabolism differ between men and women in response to laparoscopic Roux-en-Y gastric bypass (LRYGB) and compare the effects of LRYGB to the effect of a 7-week Very-Low Caloric Diet (VLCD) induced weight loss. METHODS Fasting serum IPA concentration was measured in 121 individuals from the ongoing Kuopio OBesity Surgery study (KOBS, 36 men and 85 women; BMI 42.9 ± 5.3 kg/m2) at both baseline and 1-year follow-up visits using targeted LC-QQQ-MS. In addition, plasma IPA levels were measured in 78 participants of Foods for weight management study (ELIPA, 21 men and 57 women, BMI 34.2 ± 2.6 kg/m2) by non-targeted LC-QTOF-MS metabolite profiling. RESULTS Male and female participants of the KOBS were similar in age, BMI, and IPA concentrations at baseline. We observed an increase in IPA in women but not in men in response to RYGB (P = 0.028 for 1-year follow-up vs. sex interaction). This increase in IPA was associated with decreased fasting plasma insulin, independently of weight loss. Conversely, VLCD intervention induced a similar increase in IPA in both women and men, and changes in IPA did not correlate with change in plasma insulin. CONCLUSION Our results suggest that LRYGB-induced increase in serum IPA concentration in women may be associated with decrease in fasting insulin. A comprehensive understanding of the sex-specific effects responses of the IPA to LRYGB could improve targeting non-surgical and surgical treatments to men and women.