Food Intake and Eating Behavior After Bariatric Surgery

Bile acids are physiological detergents that generate bile flow and facilitate intestinal absorption and transport of lipids, nutrients, and vitamins. Bile acids also are signaling molecules and inflammatory agents that rapidly activate nuclear receptors and cell signaling pathways that regulate lipid, glucose, and energy metabolism. The enterohepatic circulation of bile acids exerts important physiological functions not only in feedback inhibition of bile acid synthesis but also in control of whole-body lipid homeostasis. In the liver, bile acids activate a nuclear receptor, farnesoid X receptor (FXR), that induces an atypical nuclear receptor small heterodimer partner, which subsequently inhibits nuclear receptors, liver-related homolog-1, and hepatocyte nuclear factor 4alpha and results in inhibiting transcription of the critical regulatory gene in bile acid synthesis, cholesterol 7alpha-hydroxylase (CYP7A1). In the intestine, FXR induces an intestinal hormone, fibroblast growth factor 15 (FGF15; or FGF19 in human), which activates hepatic FGF receptor 4 (FGFR4) signaling to inhibit bile acid synthesis. However, the mechanism by which FXR/FGF19/FGFR4 signaling inhibits CYP7A1 remains unknown. Bile acids are able to induce FGF19 in human hepatocytes, and the FGF19 autocrine pathway may exist in the human livers. Bile acids and bile acid receptors are therapeutic targets for development of drugs for treatment of cholestatic liver diseases, fatty liver diseases, diabetes, obesity, and metabolic syndrome.

Nutritional deprivation suppresses immune function. The cloning of the obese gene and identification of its protein product leptin has provided fundamental insight into the hypothalamic regulation of body weight. Circulating levels of this adipocyte-derived hormone are proportional to fat mass but maybe lowered rapidly by fasting or increased by inflammatory mediators. The impaired T-cell immunity of mice now known to be defective in leptin (ob/ob) or its receptor (db/db), has never been explained. Impaired cell-mediated immunity and reduced levels of leptin are both features of low body weight in humans. Indeed, malnutrition predisposes to death from infectious diseases. We report here that leptin has a specific effect on T-lymphocyte responses, differentially regulating the proliferation of naive and memory T cells. Leptin increased Th1 and suppressed Th2 cytokine production. Administration of leptin to mice reversed the immunosuppressive effects of acute starvation. Our findings suggest a new role for leptin in linking nutritional status to cognate cellular immune function, and provide a molecular mechanism to account for the immune dysfunction observed in starvation.

Metabolic/bariatric procedures for the treatment of morbid obesity, as well as for type 2 diabetes, are among the most commonly performed gastrointestinal operations today, justifying periodic assessment of the numerical status of metabolic/bariatric surgery and its relative distribution of procedures. An email questionnaire was sent to the leadership of the 50 nations or national groupings in the International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO). Outcome measurements were numbers of metabolic/bariatric operations and surgeons, types of procedures performed, and trends from 2003 to 2008 to 2011 worldwide and in the regional groupings of Europe, USA/Canada, Latin/South America, and Asia/Pacific. Response rate was 84%. The global total number of procedures in 2011 was 340,768; the global total number of metabolic/bariatric surgeons was 6,705. The most commonly performed procedures were Roux-en-Y gastric bypass (RYGB) 46.6%; sleeve gastrectomy (SG) 27.8%; adjustable gastric banding (AGB) 17.8%; and biliopancreatic diversion/duodenal switch (BPD/DS) 2.2%. The global trends from 2003 to 2008 to 2011 showed a decrease in RYGB: 65.1 to 49.0 to 46.6%; an increase, followed by a steep decline, in AGB: 24.4 to 42.3 to 17.8%; and a marked increase in SG: 0.0 to 5.3 to 27.89%. BPD/DS declined: 6.1 to 4.9 to 2.1%. The trends from the four IFSO regions differed, except for the universal increase in SG. Periodic metabolic/bariatric surgery surveys add to the knowledge and understanding of all physicians caring for morbidly obese patients. The salient message of the 2011 assessment is that SG (0.0% in 2008) has markedly increased in prevalence.