Elsevier

Metabolism

Volume 58, Issue 10, October 2009, Pages 1400-1407
Metabolism

Serum bile acid along with plasma incretins and serum high–molecular weight adiponectin levels are increased after bariatric surgery

https://doi.org/10.1016/j.metabol.2009.05.006Get rights and content

Abstract

Bariatric surgery has been shown to improve glucose tolerance, although the mechanism has not been fully elucidated. Animal studies have suggested important roles of bile acid (BA) as a regulator of energy homeostasis and glucose metabolism. However, little is known about its role in humans. We investigated the longitudinal changes of BA, incretins, and adipokines after significant weight reduction in 34 Japanese adults with morbid obesity who underwent laparoscopic bariatric surgery. In subjects who underwent malabsorptive or restrictive surgery, body mass index had markedly decreased from 43.0 ± 6.5 (SD) to 37.8 ± 5.7 kg/m2 and from 45.3 ± 11.2 to 41.5 ± 10.5 kg/m2, respectively, at 1 month after surgery. Glycated hemoglobin decreased from 6.1% ± 1.5% to 5.2% ± 0.4% and from 6.2% ± 1.3% to 5.4% ± 0.7%, and total BA level increased from 3.1 ± 3.5 to 7.2 ± 5.3 μmol/L and from 3.2 ± 2.6 to 9.4 ± 10.0 μmol/L, respectively. At baseline, serum concentration of primary BA was positively correlated with plasma gastric inhibitory polypeptide level (r = 0.548, P = .001); and change in primary BA level was positively correlated with changes in plasma gastric inhibitory polypeptide (r = 0.626, P = .001) and serum immunoreactive insulin level (r = 0.592, P = .002) at 1 month after surgery. Furthermore, plasma glucagon-like peptide–1 and serum high–molecular weight adiponectin levels increased in both surgeries. These hormonal changes might explain the mechanism(s) of improved glucose tolerance after bariatric surgery in morbidly obese subjects.

Introduction

Type 2 diabetes mellitus (T2DM) is a major global health problem, causing a number of complications including microangiopathy and cardiovascular disease. It is now clear that strict control of hyperglycemia in patients with T2DM can attenuate the development of such complications. At present, several hypoglycemic agents are available, such as sulfonylureas, metformin, thiazolidinediones, α-glucosidase inhibitors, and insulin. Because these agents are mainly intended to reduce hyperglycemia itself and have limited efficacy, further approaches are needed for the treatment of T2DM.

One of the most important contributors to the pathogenesis of T2DM is obesity. In patients with morbid obesity, bariatric surgery is currently the most effective treatment to achieve long-term weight reduction. It is also reported that long-term total mortality is significantly reduced after gastric bypass surgery, particularly death from heart disease, cancer, and diabetes [1], [2]. Most interestingly, resolution of T2DM has been reported after bariatric surgery [3]; and amelioration of glycemic control often occurs before significant weight reduction [4], suggesting that the improvement in glycemic control might be related to a direct effect of bariatric surgery rather than weight reduction. A clear understanding of the short-term improvement in glycemic control after bariatric surgery might lead to a new strategy for the treatment of T2DM. It has been proposed that the incretins [5] and/or adiponectin [6] may be key mediators of the antidiabetic effects of bariatric surgery. However, the mechanism has not been fully elucidated.

Recently, we have reported that bile acid (BA) lowers the triglyceride (TG) level [7] and, moreover, induces energy expenditure by promoting intracellular thyroid hormone activation in mice [8]. Although BA has long been known to be essential for dietary lipid absorption and cholesterol catabolism, an important role of BA as a regulator of energy homeostasis has emerged. We hypothesized that bariatric surgery might change the concentration of BA and that this may be related to the mechanism for amelioration of T2DM, at least in part.

The purpose of the present study was to clarify the association between BA and metabolic parameters. We measured serum BA concentration in 34 patients with morbid obesity and investigated its correlation with metabolic parameters, adipokines, and incretins. Furthermore, we studied the longitudinal change in BA, adipokines, and incretins after laparoscopic bariatric surgery.

Section snippets

Subjects

Sixteen male and 18 female morbidly obese patients (aged 39 ± 9 years) undergoing laparoscopic bariatric surgery at Yotsuya Medicalcube Hospital (Tokyo, Japan) were recruited. We defined laparoscopic Roux-en-Y gastric bypass surgery (LRYGB) and laparoscopic sleeve gastrectomy with duodenal jejunal bypass surgery (LSG/DJB) as malabsorptive procedures (MP), and laparoscopic sleeve gastrectomy (LSG) and laparoscopic adjustable gastric banding (LAGB) as restrictive procedures (RP). Four men and 15

Baseline clinical characteristics and relationships between BA and clinical parameters

Relationships between BA and anthropometric and metabolic parameters, adipokines, and incretins in the 34 patients are shown in Table 1. Serum total BA level was 3.2 ± 3.1 μmol/L (range, 0.4-15.5 μmol/L). Total and primary BA levels were positively correlated with plasma GIP level. These correlations were significant even after adjustment for BMI (r = 0.549, P = .001 and r = 0.613, P < .001, respectively).

Among endocrine parameters measured, HMW adiponectin was negatively correlated with both

Discussion

In this study, we have shown that (1) serum BA, serum HMW adiponectin, and plasma GLP-1 levels were increased after both MP and RP; (2) plasma GIP level increased after RP; (3) serum primary BA level was positively correlated with plasma GIP level, and the change in BA level after surgery was positively correlated with the changes in GIP level (at both 1 and 3 months) and IRI (at 1 month) after surgery; and (4) the change in HMW adiponectin was negatively correlated with the change in HOMA-IR

Acknowledgment

We are particularly grateful to all the individuals who participated in this study. This study was supported in part by research grants (to M.W. and H.H.) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

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