Page 72 - Human Bile Acid Metabolism: a Postprandial Perspective

Chapter 4
and glucagon-like peptide-1 (GLP-1) from enteroendocrine L-cells, respectively [11-13]. In turn, FGF19 suppresses hepatic BA synthesis and gluconeogenesis via the FGF receptor 4 (FGFR4). GLP-1 increases the amount of insulin that is released by the pancreatic beta cell in response to glucose [14] making it useful in diabetes therapy. Possibly, BA can also directly stimulate beta cell insulin release via both FXR and TGR5 [15,16].
Is had been shown that postprandial circulating glycine-conjugated BAs are lower in obese subjects, but it is unknown whether this is reversible [3]. We assessed the effects of a twoweek very low calorie diet (VLCD) weight loss intervention on fasting and postprandial plasma BA profiles.
Materials and methods
Subjects
We recruited a total of 12 male and female insulin resistant obese subjects (HOMA- IR >2.7, BMI >30 kg/m2, age 18-55 years). Exclusion criteria were any previous surgery or current diseases of the liver, biliary or gastrointestinal tract; ethanol abuse; weight loss or weight gain in excess of 10% of body weight in the 6 months prior to start of the study; use of any medication or herbal supplement; fasting plasma glucose >7.0 mmol/L, HbA1c > 53 mmol/mol, creatinine >120 mM, or abnormal renal, liver or thyroid function defined as >2 times the upper limit of the reference interval. Written informed consent was obtained from all subjects before start of the study. The study was approved by the AMC Medical Ethics Committee. The study was conducted in accordance with the principles of the Declaration of Helsinki (sixth revision, 2008).
Hypocaloric VLCD diet
Subjects were instructed to follow a 450 kcal/day diet for 14 days. The diet consisted of 3 sachets of a liquid meal replacement formula (Modifast Intensive®, Nutrition et Sante´, France). Modifast Intensive® is a commercially available diet product, supplying 51% of energy as carbohydrates, 20% as protein and 29% as fat. Subjects were encouraged to complement the diet with low-caloric raw vegetables. Daily phone calls were conducted by the investigators to ensure diet compliance.
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