ABSTRACT
BACKGROUND: 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. 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). METHODS: Obese 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. RESULTS: All 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). CONCLUSIONS: Elevated 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.
Subject(s)
Bariatric Surgery/methods , Diabetes Mellitus, Type 2/metabolism , Fibroblast Growth Factors/metabolism , Mitochondria/metabolism , Obesity/metabolism , Adult , Diabetes Mellitus, Type 2/pathology , Female , Humans , Middle Aged , Obesity/pathology , Obesity/therapy , Prospective StudiesABSTRACT
Excessive accumulation of body fat triggers insulin resistance and features of the metabolic syndrome. Recently, evidence has accumulated that obesity, type 2 diabetes, and metabolic syndrome are associated with reduced levels of serum prolactin (PRL) in humans and rodents, raising the question of whether low PRL levels contribute to metabolic dysfunction. Here, we have addressed this question by investigating the role of PRL in insulin sensitivity and adipose tissue fitness in obese rodents and humans. In diet-induced obese rats, treatment with PRL delivered via osmotic mini-pumps, improved insulin sensitivity, prevented adipocyte hypertrophy, and reduced inflammatory cytokine expression in visceral fat. PRL also induced increased expression of Pparg and Xbp1s in visceral adipose tissue and elevated circulating adiponectin levels. Conversely, PRL receptor null mice challenged with a high-fat diet developed greater insulin resistance, glucose intolerance, and increased adipocyte hypertrophy compared with wild-type mice. In humans, serum PRL values correlated positively with systemic adiponectin levels and were reduced in insulin-resistant patients. Furthermore, PRL circulating levels and PRL produced by adipose tissue correlated directly with the expression of PPARG, ADIPOQ, and GLUT4 in human visceral and sc adipose tissue. Thus, PRL, acting through its cognate receptors, promotes healthy adipose tissue function and systemic insulin sensitivity. Increasing the levels of PRL in the circulation may have therapeutic potential against obesity-induced metabolic diseases.
Subject(s)
Adipose Tissue/metabolism , Insulin Resistance , Obesity/blood , Prolactin/therapeutic use , Adiponectin/blood , Adiponectin/metabolism , Adult , Animals , Biomarkers/metabolism , Diet, High-Fat/adverse effects , Homeostasis , Humans , Intra-Abdominal Fat/metabolism , Male , Mice, Inbred C57BL , Obesity/etiology , PPAR gamma/metabolism , Prolactin/blood , Rats, Wistar , X-Box Binding Protein 1/metabolismABSTRACT
The hormone prolactin (PRL), fundamental for lactation in mammals, is known to exert a wide diversity of actions in the various vertebrate groups. Blood vessels are surfacing as important PRL targets, contributing to these hormonal functions. PRL promotes the growth of new blood vessels (angiogenesis) and is proteolytically cleaved to vasoinhibins, a family of peptides (including 16-kDa PRL) with potent antiangiogenic and blood vessel regression effects. These opposing actions point to the regulation of the proteases responsible for PRL cleavage as an efficient way to balance blood vessel growth and involution. This review briefly summarizes the effects of PRL and vasoinhibins on blood vessels in mammals and discusses whether similar vascular actions could contribute to the effects of PRL on the development, growth, and reproduction of lower vertebrates. A comparative study in diverse species may lead to a better understanding of blood vessels as a driving force for the biological actions of PRL.