Serum bile acid along with plasma incretins and serum high–molecular weight adiponectin levels are increased after bariatric surgery
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.
References (27)
- et al.
A novel enzyme-linked immunosorbent assay specific for high-molecular-weight adiponectin
J Lipid Res
(2006) - et al.
Bile acids promote glucagon-like peptide–1 secretion through TGR5 in a murine enteroendocrine cell line STC-1
Biochem Biophys Res Commun
(2005) Steady-state kinetics of serum bile acids in healthy human subjects: single and dual isotope techniques using stable isotopes and mass spectrometry
J Lipid Res
(1987)- et al.
Adiponectin and protection against type 2 diabetes mellitus
Lancet
(2003) - et al.
Effects of bariatric surgery on mortality in Swedish obese subjects
N Engl J Med
(2007) - et al.
Long-term mortality after gastric bypass surgery
N Engl J Med
(2007) - et al.
Bariatric surgery: systematic review and meta-analysis
JAMA
(2004) - et al.
Reversibility of insulin resistance in obese diabetic patients: role of plasma lipids
Diabetologia
(1997) - et al.
Incretin levels and effect are markedly enhanced one month after Roux-en-Y gastric bypass surgery in obese patients with type 2 diabetes
Diabetes Care
(2007) - et al.
Circulating concentrations of high-molecular-weight adiponectin are increased following Roux-en-Y gastric bypass surgery
Diabetologia
(2006)
Bile acids lower triglyceride levels via a pathway involving FXR, SHP, and SREBP-1c
J Clin Invest
Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation
Nature
Has laparoscopic bariatric surgery been accepted in Japan? The experience of a single surgeon
Obes Surg
Cited by (164)
The emerging role of bile acids in white adipose tissue
2023, Trends in Endocrinology and MetabolismThe impact of bariatric surgery on colorectal cancer risk
2023, Surgery for Obesity and Related DiseasesRegulation of body weight: Lessons learned from bariatric surgery
2023, Molecular MetabolismEvidence-Based Nutrition and Clinical Evidence of Bioactive Foods in Human Health and Disease
2021, Evidence-Based Nutrition and Clinical Evidence of Bioactive Foods in Human Health and DiseaseTen-year remission rates in insulin-treated type 2 diabetes after biliopancreatic diversion with duodenal switch
2020, Surgery for Obesity and Related DiseasesIs bariatric surgery resolving NAFLD via microbiota-mediated bile acid ratio reversal? A comprehensive review
2020, Surgery for Obesity and Related Diseases