期刊论文详细信息
Nutrition & Metabolism
Fasting plasma chenodeoxycholic acid and cholic acid concentrations are inversely correlated with insulin sensitivity in adults
Michel Krempf3  Martine Laville2  Béatrice Guyomarc'h-Delasalle3  Emmanuel Disse2  Etienne Pouteau1  Yassine Zaïr3  Maud Chetiveaux3  Bertrand Cariou3 
[1] Nestlé Research Center, R&D Santiago, 9260075 Maipú Santiago, Chile;CRNH Rhone-Alpes; INSERM Unit -1060, CarMeN Laboratory and CENS, Lyon1 University; Hospices Civils de Lyon, France Centre Hospitalier Lyon-Sud, F-69310 Pierre Bénite, France;INSERM, UMR915; Université de Nantes; CHU Nantes, Clinique d'Endocrinologie, Maladies Métaboliques et Nutrition, l'Institut du Thorax, Nantes, CRNH Nantes, F-44000 France
关键词: hyperinsulinemic-euglycemic clamp;    energy expenditure;    TGR5;    FXR;    type 2 diabetes;    insulin resistance;    bile acids;   
Others  :  821067
DOI  :  10.1186/1743-7075-8-48
 received in 2011-05-17, accepted in 2011-07-07,  发布年份 2011
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【 摘 要 】

Background

Accumulating data suggest a novel role for bile acids (BAs) in modulating metabolic homeostasis. BA treatment has been shown to improve glucose tolerance and to increase energy expenditure in mice. Here, we investigated the relationship between fasting plasma BAs concentrations and metabolic parameters in humans.

Findings

Fasting plasma glucose, insulin and lipid profile were measured in 14 healthy volunteers, 20 patients with type 2 diabetes (T2D), and 22 non-diabetic abdominally obese subjects. Insulin sensitivity was also assessed by the determination of the glucose infusion rate (GIR) during a hyperinsulinemic-euglycemic clamp in a subgroup of patients (9 healthy and 16 T2D subjects). Energy expenditure was measured by indirect calorimetry. Plasma cholic acid (CA), chenodeoxycholic acid (CDCA) and deoxycholic acid (DCA) concentrations were analyzed by gas chromatograph-mass spectrometry. In univariable analysis, a positive association was found between HOMA-IR and plasma CDCA (β = 0.09, p = 0.001), CA (β = 0.03, p = 0.09) and DCA concentrations (β = 0.07, p < 0.0001). Spearman analysis retrieved an inverse relationship between plasma CDCA (r = -0.44, p = 0.03), CA (r = -0.65, p = 0.001) and the GIR. HOMA-IR remained positively associated with CDCA (β = 0.11, p = 0.01), CA (β = 0.04, p = 0.01) and DCA (β = 0.06, p = 0.007) in multivariable analysis, after adjustment for age, gender, BMI, HbA1C and plasma lipid parameters. In contrast, HbA1c, energy expenditure and plasma lipid concentrations were not correlated with plasma BAs levels in multivariable analysis.

Conclusions

Both plasma CDCA, CA and DCA concentrations were negatively associated with insulin sensitivity in a wide range of subjects.

【 授权许可】

   
2011 Cariou et al; licensee BioMed Central Ltd.

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【 参考文献 】
  • [1]Lefebvre P, Cariou B, Lien F, Kuipers F, Staels B: Role of bile acids and bile acid receptors in metabolic regulation. Physiol Rev 2009, 89:147-91.
  • [2]Sinal CJ, Tohkin M, Miyata M, Ward JM, Lambert G, Gonzalez FJ: Targeted disruption of the nuclear receptor FXR/BAR impairs bile acid and lipid homeostasis. Cell 2000, 102:731-44.
  • [3]Kok T, Hulzebos CV, Wolters H, Havinga R, Agellon LB, Steellaard F, Shan B, Schwarz M, Kuipers F: Enterohepatic circulation of bile salts in farnesoid × receptor-deficient mice: efficient intestinal bile salt absorption in the absence of ileal bile acid-binding protein. J Biol Chem 2003, 278:41930-7.
  • [4]Cariou B, Staels B: FXR: a promising target for the metabolic syndrome? Trends Pharmacol Sci 2007, 5:236-43.
  • [5]Duran-Sandoval D, Cariou B, Fruchart JC, Staels B: Potential regulatory role of the farnesoid × receptor in the metabolic syndrome. Biochimie 2005, 87:93-8.
  • [6]Cariou B, van Harmelen K, Duran-Sandoval D, van Dijk TH, Grefhorst A, Abdelkarim M, Caron S, Torpier G, Fruchart JC, Gonzalez FJ, Kuipers F, Staels B: The farnesoid × receptor modulates adiposity and peripheral insulin sensitivity in mice. J Biol Chem 2006, 281:11039-49.
  • [7]Ma K, Saha PK, Chan L, Moore DD: Farnesoid × receptor is essential for normal glucose homeostasis. J Clin Invest 2006, 116:1102-9.
  • [8]Zhang Y, Lee FY, Barrera G, Lee H, Vales C, Gonzalez FJ, Willson TM, Edwards PA: Activation of the nuclear receptor FXR improves hyperglycemia and hyperlipidemia in diabetic mice. Proc Natl Acad Sci USA 2006, 103:1006-11.
  • [9]Prawitt J, Abdelkarim M, Stroeve JH, Popescu I, Duez H, Velagapudi VR, Dumont J, Bouchaert E, van Dijk TH, Lucas A, Dorchies E, Daoudi M, Lestavel S, Gonzalez FJ, Oresic M, Cariou B, Kuipers F, Caron S, Staels B: Farnesoid × receptor deficiency improves glucose homeostasis in mouse models of obesity. Diabetes 2011, 60:1861-71.
  • [10]Watanabe M, Houten SM, Mataki C, Christoffolete MA, Kim BW, Sato H, Messaddeq N, Harney JW, Ezaki O, Kodama T, Schoonjans K, Bianco AC, Auwerx J: Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation. Nature 2006, 439:484-9.
  • [11]Maruyama T, Miyamoto Y, Nakamura T, Tamai Y, Okada H, Sugiyama E, Nakamura T, Itadani H, Tanaka K: Identification of membrae-type receptor for bile acids (M-BAR). Biochem Biophys Res Commun 2002, 298:714-719.
  • [12]Kawamata Y, Fujii R, Hosoya M, Harada M, Yoshida H, Miwa M, Fukusumi S, Habata Y, Itoh T, Shintani Y, Hinuma S, Fujisawa Y, Fujino M: A G protein-coupled receptor responsive to bile acids. J Biol Chem 2003, 278:9435-40.
  • [13]Thomas C, Gioiello A, Noriega L, Strehle A, Oury J, Rizzo G, Macchiarulo A, Yamamoto H, Mataki C, Pruzanski M, Pellicciari R, Auwerx J, Schoonjans K: TGR5-mediated bile acid sensing controls glucose homeostasis. Cell Metab 2009, 10:167-77.
  • [14]Stellaard F, Langelaar SA, Kok RM, Jakobs C: Determination of plasma bile acids by capillary gas-liquid chromatography-electron capture negative chemical ionization mass fragmentography. J Lipid Res 1998, 30:1647-52.
  • [15]DeFronzo RA, Tobin JD, Andres R: Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol 1979, 237:E214-E223.
  • [16]Sanyal AJ, Mudaliar S, Henry RR, Marschall HU, Morrow L, Sciacca CI, Dillon P, Clopton P, Kipnes M, Shapiro D: A new therapy for nonalcoholic fatty liver disease and diabetes? INT-747-the first FXR hepatic therapeutic study. Hepatology 2009, 50(Suppl S):389-390A.
  • [17]Bennion LJ, Grundy SM: Effects of diabetes mellitus on cholesterol metabolism in man. N Engl J Med 1997, 296:1365-71.
  • [18]Abrams JJ, Ginsberg H, Grundy SM: Metabolism of cholesterol and plasma triglycerides in nonketotic diabetes mellitus. Diabetes 1982, 31:903-10.
  • [19]Brufau G, Stellaard F, Prado K, Bloks VW, Jonkers E, Boverhof R, Kuipers F, Murphy E: Improved glycemic control with colesevelam treatment in patients with type 2 diabetes is not directly associated with changes in bile acid metabolism. Hepatology 2010, 52:1455.
  • [20]Staels B, Kuipers F: Bile acid sequestrants and the treatment of type 2 diabetes mellitus. Drugs 2007, 67:1383-92.
  • [21]Shaham O, Wei R, Wang TJ, Ricciardi C, Lewis GD, Vasan RS, Carr SA, Thadhani R, Gerszten RE, Mootha VK: Metabolic profiling of the human response to a glucose challenge reveals distinct axes of insulin sensitivity. Mol Syst Biol 2008, 4:214.
  • [22]Brufau G, Bahr MJ, Staels B, Claudel T, Ockenga J, Böker KH, Murphy EJ, Prado K, Stellaard F, Manns MP, Kuipers F, Tietge UJ: Plasma bile acids are not associated with energy metabolism in humans. Nutr Metab (Lond) 2010, 7:73. BioMed Central Full Text
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