Abstract
BackgroundThe ileal-derived hormone, fibroblast growth factor 19 (FGF-19), may promote weight loss and facilitate type-2 diabetes mellitus remission in bariatric surgical patients. We investigated the effect of different bariatric procedures on circulating FGF-19 levels and the resulting impact on mitochondrial health in white adipose tissue (AT).MethodsObese and type-2 diabetic women (n = 39, BMI > 35 kg/m2) undergoing either biliopancreatic diversion (BPD), laparoscopic greater curvature plication (LGCP), or laparoscopic adjustable gastric banding (LAGB) participated in this ethics approved study. Anthropometry, biochemical, clinical data, serum, and AT biopsies were collected before and 6 months after surgery. Mitochondrial gene expression in adipose biopsies and serum FGF-19 levels were then assessed.ResultsAll surgeries led to metabolic improvements with BPD producing the greatest benefits on weight loss (↓30%), HbA1c (↓28%), and cholesterol (↓25%) reduction, whilst LGCP resulted in similar HbA1c improvements (adjusted for BMI). Circulating FGF-19 increased in both BPD and LGCP (χ2(2) = 8.088; P = 0.018), whilst, in LAGB, FGF-19 serum levels decreased (P = 0.028). Interestingly, circulating FGF-19 was inversely correlated with mitochondrial number in AT across all surgeries (n = 39). In contrast to LGCP and LAGB, mitochondrial number in BPD patients corresponded directly with changes in 12 of 14 mitochondrial genes assayed (P < 0.01).ConclusionsElevated serum FGF-19 levels post-surgery were associated with improved mitochondrial health in AT and overall diabetic remission. Changes in circulating FGF-19 levels were surgery-specific, with BPD producing the best metabolic outcomes among the study procedures (BPD > LGCP > LAGB), and highlighting mitochondria in AT as a potential target of FGF-19 during diabetes remission.
Highlights
The ileal-derived hormone, fibroblast growth factor 19 (FGF-19), may promote weight loss and facilitate type-2 diabetes mellitus remission in bariatric surgical patients
Bariatric surgery involves a type/degree of gastro-intestinal remodelling, which can lead to reduced stomach volume and nutrient absorption capacity [20, 21]; this alone cannot fully explain the profound weight loss and metabolic improvement observed after these surgeries versus medical/lifestyle interventions [22]
In the present study, we investigated the hypothesis that changes in serum FGF-19 levels after bariatric surgery support metabolic recovery via improvement in mitochondrial function within white adipose tissue (AT)
Summary
The ileal-derived hormone, fibroblast growth factor 19 (FGF-19), may promote weight loss and facilitate type-2 diabetes mellitus remission in bariatric surgical patients. During sustained conditions of chronic nutrient excess, such as obesity and type-2 diabetes, mitochondria appear unable to cope well with this environment, leading to fragmentation, unresponsiveness and dysfunction [5,6,7] This nutrient-induced mitochondrial dysfunction can lead to impaired respiration, lipotoxicity, oxidative species accumulation and inflammation, further exacerbating insulin resistance and type diabetes [8,9,10,11,12,13]. The importance of adequate mitochondrial function for metabolic health is further highlighted by the observation that mitochondrial DNA mutations often result in diabetic phenotypes [14,15,16] Both insulin resistance and type-2 diabetes status can be reversed through bariatric surgery, with significantly greater success rates than pharmacological, exercise and diet interventions [17,18,19]. Bariatric surgery involves a type/degree of gastro-intestinal remodelling, which can lead to reduced stomach volume and nutrient absorption capacity [20, 21]; this alone cannot fully explain the profound weight loss and metabolic improvement observed after these surgeries versus medical/lifestyle interventions [22]
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