Effects of Lacticaseibacillus rhamnosus HA-114 probiotic supplementation on circulating IGFBP-2 levels during a calorie-restricted diet in overweight humans.

Background and aim: Gut microbiota influences energy homeostasis in part through circulating hormones. Insulin-like growth factor-binding protein (IGFBP)-2 is a biomarker whose increase in systemic circulation is associated with positive effects on body weight and metabolism. In a recent clinical trial, probiotic Lacticaseibacillus rhamnosus HA-114 supplementation showed positive effects on eating behaviors and insulin resistance in overweight participants undergoing a weight-loss intervention. In this context, this ancillary study aimed at assessing the impact of L. rhamnosus HA-114 supplementation on plasma IGFBP-2 levels in these individuals, and whether this modulation correlated with changes in fat mass, energy metabolism, and eating behaviors. Methods: Fasting plasma IGFBP-2 concentrations were quantified in 100 overweight or obese men and women enrolled in a 12-week diet-based weight reduction program (-500 kcal/day), in combination with probiotic L. rhamnosus HA-114 or placebo supplementation. Baseline and changes in circulating IGFBP-2 concentrations were correlated with anthropometric parameter, glucose and lipid metabolism, cardiorespiratory function and eating behaviors. Results: On average, the intervention reduced BMI by 4.6 % and increased IGFBP-2 by 13 %, regardless of supplementation group. Individuals who presented an increase in IGFBP-2 levels had significantly greater reductions in BMI. Changes in IGFBP-2 levels were correlated with loss in fat mass (r = 0.2, p < 0.001) in the probiotic-supplemented group, but not with other metabolic parameters or eating behaviors. Baseline IGFBP-2 levels were not associated with weight loss or improvements in cardiometabolic parameters. Conclusion: Probiotic supplementation with L. rhamnosus HA-114 did not modulate plasma IGFBP-2 levels. Changes in IGFBP-2 levels were correlated with greater reductions in BMI, but not with other metabolic parameters or eating behaviors, indicating that the benefits of HA-114 on eating behaviors are likely independent of IGFBP-2. Additional changes in microbiota might be required to modulate IGFBP-2 and observe its associations with eating behaviors and cardiometabolic improvements.

IGFBP-2 partly mediates the early metabolic improvements caused by bariatric surgery.

Insulin-like growth factor-binding protein (IGFBP)-2 is a circulating biomarker of cardiometabolic health. Here, we report that circulating IGFBP-2 concentrations robustly increase after different bariatric procedures in humans, reaching higher levels after biliopancreatic diversion with duodenal switch (BPD-DS) than after Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG). This increase is closely associated with insulin sensitization. In mice and rats, BPD-DS and RYGB operations also increase circulating IGFBP-2 levels, which are not affected by SG or caloric restriction. In mice, Igfbp2 deficiency significantly impairs surgery-induced loss in adiposity and early improvement in insulin sensitivity but does not affect long-term enhancement in glucose homeostasis. This study demonstrates that the modulation of circulating IGFBP-2 may play a role in the early improvement of insulin sensitivity and loss of adiposity brought about by bariatric surgery.

Metabolic adaptations after bariatric surgery: adipokines, myokines and hepatokines.

This review addresses the impact of bariatric surgery on the endocrine aspects of white adipose tissue, muscle and the liver. We describe literature supporting the notion that adipokines, myokines and hepatokines likely act in concert and drive many of the long-term metabolic improvements following surgery. Circulating adiponectin is increased while secretion of pro-inflammatory interleukins (1, 6 and 8) decreases, alongside leptin secretion. The metabolic improvements observed in the muscle might relate to reduction of myokines contributing to insulin resistance (including myostatin, brain-derived neurotrophic factor and fibroblast growth factor-21). Subject to exception, hepatokine secretion is generally increased (such as insulin-like growth factor-binding protein 2, adropin and sex hormone-binding globulin). In conclusion, bariatric surgery restores metabolic functions by enhancing the time-dependent secretion of anti-inflammatory, insulin-sensitizing and antilipemic factors. Further research is needed to understand the molecular mechanisms by which these factors may trigger the remission of obesity-related comorbidities following bariatric surgery.