One anastomosis mini-gastric bypass decreases desacyl ghrelin and improves metabolic profile in male rats with diet-induced obesity

The potential participation of acylated ghrelin (AG) and Desacyl ghrelin (DAG) in insulin resistance improvement following one anastomosis mini-gastric bypass (OAGB) remains unknown. This study compares the efficacy of the OAGB and caloric restriction in the treatment of obesity and evaluates the relationship between ghrelin isoforms and insulin sensitivity post-intervention. To that end, 40 rats were used in the experimental design, 37 rats with diet-induced obesity (DIO) were subjected to either Sham (n=11), OAGB (n=6) or dietary interventions (fed ad libitum a normal diet [n=6], a high-fat diet [n=6] or pair-fed (PFD) to the amount of food eaten by the OAGB rats [n=8]). The OAGB surgery resulted in significant and sustained weight loss, supported by a lower body weight (P<.01) and total adiposity compared to Sham-operated and PFD controls (P<.05 for all). Although the OAGB did not lead to significant differences in relative food intake, it induced a lower food efficiency ratio (FER) (P<.01), higher rectal temperatures (P<.05), and increased Pgc1a gene expression levels (P<.05) in brown adipose tissue (BAT), suggesting an improved energy expenditure. The OAGB also ameliorated insulin sensitivity, as evidenced by a decreased plasma glucose (P<.05), insulin (P<.01) and homeostasis model assessment of insulin resistance HOMA-IR (P<.05) compared to caloric-restricted rats, without affecting the lipid profile. Plasma DAG levels significantly decreased (P<.05) one month after the OAGB, and significant correlations were observed between DAG and markers of insulin resistance, including insulin, HOMA-IR, leptin, and adipose insulin resistance index (Adipo-IR). This study demonstrates that the OAGB leads to significant improvements in body composition and metabolic profile through mechanisms beyond caloric restriction. The effects appear to be mediated by changes in energy expenditure and adipose tissue function, potentially modulated by alterations in the gut hormone DAG.