The publication data currently available has been vetted by Vanderbilt faculty, staff, administrators and trainees. The data itself is retrieved directly from NCBI's PubMed and is automatically updated on a weekly basis to ensure accuracy and completeness.
If you have any questions or comments, please contact us.
Bariatric surgery, specifically Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG), are the most effective and durable treatments for morbid obesity and potentially a viable treatment for type 2 diabetes (T2D). The resolution rate of T2D following these procedures is between 40 and 80% and far surpasses that achieved by medical management alone. The molecular basis for this improvement is not entirely understood, but has been attributed in part to the altered enterohepatic circulation of bile acids. In this review we highlight how bile acids potentially contribute to improved lipid and glucose homeostasis, insulin sensitivity and energy expenditure after these procedures. The impact of altered bile acid levels in enterohepatic circulation is also associated with changes in gut microflora, which may further contribute to some of these beneficial effects. We highlight the beneficial effects of experimental surgical procedures in rodents that alter bile secretory flow without gastric restriction or altering nutrient flow. This information suggests a role for bile acids beyond dietary fat emulsification in altering whole body glucose and lipid metabolism strongly, and also suggests emerging roles for the activation of the bile acid receptors farnesoid x receptor (FXR) and G-protein coupled bile acid receptor (TGR5) in these improvements. The limitations of rodent studies and the current state of our understanding is reviewed and the potential effects of bile acids mediating the short- and long-term metabolic improvements after bariatric surgery is critically examined.
Copyright © 2017 Elsevier Ltd. All rights reserved.
AIMS - Ghrelin is a gastric-derived hormone that stimulates growth hormone (GH) secretion and has a multi-faceted role in the regulation of energy homeostasis, including glucose metabolism. Circulating ghrelin concentrations are modulated in response to nutritional status, but responses to ghrelin in altered metabolic states are poorly understood. We investigated the metabolic effects of ghrelin in obesity and early after Roux-en-Y gastric bypass (RYGB).
MATERIALS AND METHODS - We assessed central and peripheral metabolic responses to acyl ghrelin infusion (1 pmol kg min ) in healthy, lean subjects (n = 9) and non-diabetic, obese subjects (n = 9) before and 2 weeks after RYGB. Central responses were assessed by GH and pancreatic polypeptide (surrogate for vagal activity) secretion. Peripheral responses were assessed by hepatic and skeletal muscle insulin sensitivity during a hyperinsulinaemic-euglycaemic clamp.
RESULTS - Ghrelin-stimulated GH secretion was attenuated in obese subjects, but was restored by RYGB to a response similar to that of lean subjects. The heightened pancreatic polypeptide response to ghrelin infusion in the obese was attenuated after RYGB. Hepatic glucose production and hepatic insulin sensitivity were not altered by ghrelin infusion in RYGB subjects. Skeletal muscle insulin sensitivity was impaired to a similar degree in lean, obese and post-RYGB individuals in response to ghrelin infusion.
CONCLUSIONS - These data suggest that obesity is characterized by abnormal central, but not peripheral, responsiveness to ghrelin that can be restored early after RYGB before significant weight loss. Further work is necessary to fully elucidate the role of ghrelin in the metabolic changes that occur in obesity and following RYGB.
© 2017 John Wiley & Sons Ltd.
CONTEXT - Roux-en-Y gastric bypass (RYGB) is the most effective treatment for morbid obesity and resolution of diabetes. Over the last decade, it has become well accepted that this resolution of diabetes occurs before significant weight loss; however, the mechanisms behind this effect remain unknown and could represent novel therapeutic targets for obesity and diabetes. Bile acids have been identified as putative mediators of these weight loss-independent effects.
OBJECTIVE - To identify the longitudinal changes in bile acids after RYGB, which may provide mechanistic insight into the weight loss-independent effects of RYGB.
DESIGN - Observational study before/after intervention.
SETTING - Academic medical center.
PATIENTS/PARTICIPANTS - Samples were collected from morbidly obese patients (n = 21) before and after RYGB.
INTERVENTION - RYGB.
MAIN OUTCOME MEASURES - Seventeen individual bile acid species were measured preoperatively and at 1, 6, 12, and 24 months postoperatively. Anthropometric, hormonal, and hyperinsulinemic-euglycemic clamp data were also examined to identify physiological parameters associated with bile acid changes.
RESULTS - Fasting total plasma bile acids increased after RYGB; however, increases were bimodal and were observed only at 1 (P < .05) and 24 months (P < .01). One-month increases were secondary to surges in ursodeoxycholic acid and its glycine and taurine conjugates, bacterially derived bile acids with putative insulin-sensitizing effects. Increases at 24 months were due to gradual rises in primary unconjugated bile acids as well as deoxycholic acid and its glycine conjugate. Plasma bile acid changes were not significantly associated with any anthropometric or hormonal measures, although hepatic insulin sensitivity was significantly improved at 1 month.
CONCLUSIONS - Overall findings suggest that bacterially derived bile acids may mediate the early improvements at 1 month after RYGB. Future studies should examine the changes in specific bile acid chemical species after bariatric procedures and bile acid-specific signaling changes.
OBJECTIVE - To measure changes in resting metabolic rate (RMR) and body composition in obese subjects following massive weight loss achieved via bariatric surgery or calorie restriction plus vigorous exercise.
METHODS - Body composition and RMR were measured in 13 pairs of obese subjects retrospectively matched for sex, body mass index, weight, and age who underwent either Roux-en-Y gastric bypass surgery (RYGB) or participated in "The Biggest Loser" weight loss competition (BLC).
RESULTS - Both groups had similar final weight loss (RYGB: 40.2 ± 12.7 kg, BLC: 48.8 ± 14.9 kg; P = 0.14); however, RYGB lost a larger proportion of their weight as fat-free mass (FFM) (RYGB: 30 ± 12%, BLC: 16 ± 8% [P < 0.01]). In both groups, RMR decreased significantly more than expected based on measured body composition changes. The magnitude of this metabolic adaptation was correlated with the degree of energy imbalance (r = 0.55, P = 0.004) and the decrease in circulating leptin (r = 0.47, P = 0.02).
CONCLUSIONS - Calorie restriction along with vigorous exercise in BLC participants resulted in preservation of FFM and greater metabolic adaption compared to RYGB subjects despite comparable weight loss. Metabolic adaptation was related to the degree of energy imbalance and the changes in circulating leptin.
© 2014 The Obesity Society.
Obesity and chronic, treated HIV infection are both associated with persistent systemic inflammation and a similar constellation of metabolic and cardiovascular diseases, but the combined effects of excess adiposity and HIV on circulating proinflammatory cytokines and other biomarkers previously shown to predict disease risk is not well described. We measured inflammation biomarker levels in 158 predominantly virologically suppressed adults on long-term antiretroviral therapy (ART) with a range of body mass index (BMI) values from normal to morbidly obese. We assessed the relationship between BMI and each biomarker using multivariable linear regression adjusted for age, sex, race, CD4(+) count, tobacco use, data source, protease inhibitor use, and routine nonsteroidal antiinflammatory drug (NSAID) or aspirin use. Among normal-weight (n=48) and overweight participants (n=41; BMI <30 kg/m(2)), incremental BMI increases were associated with significantly higher serum highly sensitive C-reactive protein (hsCRP; β=2.47, p=0.02) and tumor necrosis factor (TNF)-α receptor 1 levels (β=1.53, p=0.03), and significantly lower CD14 levels (β=0.84, p=0.01), but similar associations were not observed in the obese participants. Among the obese (n=69; BMI ≥30 kg/m(2)), however, higher serum levels of interleukin-6 (IL-6; β=1.30, p=0.02) and macrophage inflammatory protein-1α (β=1.77, p<0.01) were associated with higher BMI, a finding not observed among the nonobese. Among all participants, IL-6 and TNF-α receptor 1 levels were most closely associated with hsCRP (p<0.01). Further studies are needed to determine whether higher serum inflammation biomarker levels found in obese HIV-infected individuals on ART reflect an increased likelihood of adverse health outcomes, or if novel markers to estimate mortality and disease risk are needed in this population.