Estrogen signaling prevents diet-induced hepatic insulin resistance in male mice with obesity

American Journal of Physiology - Endocrinology and Metabolism

Volumn 306, Issue 10, 2014, Pages

  Zhu, Lin ^a   Martinez, Melissa N ^a   Emfinger, Christopher H ^a   Palmisano, Brian T ^a   Stafford, John M ^a  

^a VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

And hyperinsulinemic euglycemic clamp; Estrogen; Estrogen receptor ; Insulin resistance; Liver lipid metabolism; Males; Sex differences

Indexed keywords

DIACYLGLYCEROL; ESTROGEN; ESTROGEN RECEPTOR ALPHA; GLYCOGEN; INSULIN; LIPID; PROTEIN KINASE B; TRIACYLGLYCEROL;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CARDIOVASCULAR RISK; CONTROLLED STUDY; DYSLIPIDEMIA; ENZYME PHOSPHORYLATION; ESTROGEN THERAPY; FEEDING; FEMALE; GLUCONEOGENESIS; GLUCOSE TRANSPORT; GLYCOGEN LIVER LEVEL; GLYCOGEN METABOLISM; HYPERINSULINEMIA; INSULIN RESISTANCE; INSULIN SENSITIVITY; LIPID DIET; LIPID METABOLISM; LIVER; MALE; MOUSE; MUSCLE; NONHUMAN; OBESITY; PRIORITY JOURNAL; WILD TYPE;

AND HYPERINSULINEMIC EUGLYCEMIC CLAMP; ESTROGEN; ESTROGEN RECEPTOR-Α; INSULIN RESISTANCE; LIVER LIPID METABOLISM; MALES; SEX DIFFERENCES;

ANIMALS; DIACYLGLYCEROL O-ACYLTRANSFERASE; DIET, HIGH-FAT; ESTROGEN RECEPTOR ALPHA; ESTROGENS; FEMALE; INSULIN RESISTANCE; LIVER; MALE; MICE; MICE, KNOCKOUT; OBESITY; SEX FACTORS; SIGNAL TRANSDUCTION;

EID: 84900561186     PISSN: 01931849     EISSN: 15221555     Source Type: Journal    
DOI: 10.1152/ajpendo.00579.2013     Document Type: Article

References (50)

1. Ayala JE, Bracy DP, Julien BM, Rottman JN, Fueger PT, Wasserman DH. Chronic treatment with sildenafil improves energy balance and insulin action in high fat-fed conscious mice. Diabetes 56: 1025-1033, 2007.
2. Ayala JE, Bracy DP, Mcguinness O, Wasserman DH. Considerations in the design of hyperinsulinemic-euglycemic clamps in the conscious mouse. Diabetes 55: 390-397, 2006.
3. Ayala JE, Samuel VT, Morton GJ, Obici S, Croniger CM, Shulman GI, Wasserman DH, McGuinness OP. Standard operating procedures for describing and performing metabolic tests of glucose homeostasis in mice. Dis Model Mech 3: 525-534, 2010.
4. Bonnet F, Ducluzeau PH, Gastaldelli A, Laville M, Anderwald CH, Konrad T, Mari A, Balkau B; RISC Study Group. Liver enzymes are associated with hepatic insulin resistance, insulin secretion, and glucagon concentration in healthy men and women. Diabetes 60: 1660-1667, 2011.
5. Cases S, Stone SJ, Zhou P, Yen E, Tow B, Lardizabal KD, Voelker T, Farese RV Jr. Cloning of DGAT2, a second mammalian diacylglycerol acyltransferase, and related family members. J Biol Chem 276: 38870-38876, 2001.
6. Chan TM, Exton JH. A Rapid Method for the Determination of Glycogen Content and Radioactivity in Small Quantities of Tissue or Isolated Hepatocytes. Anal Biochem 71: 96-105, 1976.
7. Davis KE, D Neinast M, Sun K, M Skiles W, D Bills J, A Zehr J, Zeve D, D Hahner L, W Cox D, M Gent L, Xu Y, Wang Z, Khan S, Clegg DJ. The sexually dimorphic role of adipose and adipocyte estrogen receptors in modulating adipose tissue expansion, inflammation, and fibrosis. Mol Metab 2: 227-242, 2013.
8. Della Torre S, Rando G, Meda C, Stell A, Chambon P, Krust A, Ibarra C, Magni P, Ciana P, Maggi A. Amino acid-dependent activation of liver estrogen receptor alpha integrates metabolic and reproductive functions via IGF-1. Cell Metab 13: 205-214, 2011.
9. Dupont S, Krust A, Gansmuller A, Dierich A, Chambon P, Mark M. Effect of single and compound knockouts of estrogen receptors alpha (ERalpha) and beta (ERbeta) on mouse reproductive phenotypes. Development 127: 4277-4291, 2000.
10. Fabbrini E, Magkos F, Mohammed BS, Pietka T, Abumrad NA, Patterson BW, Okunade A, Klein S. Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity. Proc Natl Acad Sci USA 106: 15430-15435, 2009.
11. Finan B, Yang B, Ottaway N, Stemmer K, Müller TD, Yi CX, Habegger K, Schriever SC, García-Cáceres C, Kabra DG, Hembree J, Holland J, Raver C, Seeley RJ, Hans W, Irmler M, Beckers J, de Angelis MH, Tiano JP, Mauvais-Jarvis F, Perez-Tilve D, Pfluger P, Zhang L, Gelfanov V, DiMarchi RD, Tschöp MH. Targeted estrogen delivery reverses the metabolic syndrome. Nat Med 18: 1847-1856, 2012.
12. Finkelstein JS, Lee H, Burnett-Bowie SA, Pallais JC, Yu EW, Borges LF, Jones BF, Barry CV, Wulczyn KE, Thomas BJ, Leder BZ. Gonadal steroids and body composition, strength, and sexual function in men. N Engl J Med 369: 1011-1022, 2013.
13. Fox CS, Yang Q, Cupples LA, Guo CY, Atwood LD, Murabito JM, Levy D, Mendelsohn ME, Housman DE, Shearman AM. Sex-specific association between estrogen receptor-alpha gene variation and measures of adiposity: the Framingham Heart Study. J Clin Endocrinol Metab 90: 6257-6262, 2005.
14. Freedman DS, Otvos JD, Jeyarajah EJ, Shalaurova I, Cupples LA, Parise H, D'Agostino RB, Wilson PW, Schaefer EJ. Sex and age differences in lipoprotein subclasses measured by nuclear magnetic resonance spectroscopy: the Framingham Study. Clin Chem 50: 1189-1200, 2004.
15. Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Borden WB, Bravata DM, Dai S, Ford ES, Fox CS, Franco S, Fullerton HJ, Gillespie C, Hailpern SM, Heit JA, Howard VJ, Huffman MD, Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Magid D, Marcus GM, Marelli A, Matchar DB, McGuire DK, Mohler ER, Moy CS, Mussolino ME, Nichol G, Paynter NP, Schreiner PJ, Sorlie PD, Stein J, Turan TN, Virani SS, Wong ND, Woo D, Turner MB; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics-2013 update: a report from the American Heart Association. Circulation 127: e6-e245, 2013.
16. Handgraaf S, Riant E, Fabre A, Waget A, Burcelin R, Liere P, Krust A, Chambon P, Arnal JF, Gourdy P. Prevention of obesity and insulin resistance by estrogens requires ERα activation function-2 (ERαAF-2), whereas ERαAF-1 is dispensable. Diabetes 62: 4098-4108, 2013.
17. Hanley AJ, Williams K, Festa A, Wagenknecht LE, D'Agostino RB Jr, Kempf J, Zinman B, Haffner SM; insulin resistance atherosclerosis study. Elevations in markers of liver injury and risk of type 2 diabetes: the insulin resistance atherosclerosis study. Diabetes 53: 2623-2632, 2004.
18. Hwang JH, Perseghin G, Rothman DL, Cline GW, Magnusson I, Petersen KF, Shulman GI. Impaired net hepatic glycogen synthesis in insulin-dependent diabetic subjects during mixed meal ingestion. A 13C nuclear magnetic resonance spectroscopy study. J Clin Invest 95: 783-787, 1995.
19. Kim JH, Meyers MS, Khuder SS, Abdallah SL, Muturi HT, Russo L, Tate CR, Hevener AL, Najjar SM, Leloup C, Mauvais-Jarvis F. Tissue-selective estrogen complexes with bazedoxifene prevent metabolic dysfunction in female mice. Mol Metab 3: 177-190, 2014.
20. Krssak M, Brehm A, Bernroider E, Anderwald C, Nowotny P, Man CD, Cobelli C, Cline GW, Shulman GI, Waldhäusl W, Roden M. Alterations in postprandial hepatic glycogen metabolism in type 2 diabetes. Diabetes 53: 3048-3056, 2004.
21. Linnér C, Svartberg J, Giwercman A, Giwercman YL. Estrogen receptor alpha single nucleotide polymorphism as predictor of diabetes type 2 risk in hypogonadal men. Aging Male 16: 52-57, 2013.
22. Lloyd-Jones D, Adams R, Carnethon M, De Simone G, Ferguson T, Flegal K, Ford E, Furie K, Go A, Greenlund K, Haase N, Hailpern S, Ho M, Howard V, Kissela B, Kittner S, Lackland D, Lisabeth L, Marelli A, Mcdermott M, Meigs J, Mozaffarian D, Nichol G, O'donnell C, Roger V, Rosamond W, Sacco R, Sorlie P, Stafford R, Steinberger J, Thom T, Wasserthiel-Smoller S, Wong N, Wylie-Rosett J, Hong Y. Heart disease and stroke statistics-2009 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 119: e21-e181, 2009.
23. Maffei L, Murata Y, Rochira V, Tubert G, Aranda C, Vazquez M, Clyne CD, Davis S, Simpson ER, Carani C. Dysmetabolic syndrome in a man with a novel mutation of the aromatase gene: effects of testosterone, alendronate, and estradiol treatment. J Clin Endocrinol Metab 89: 61-70, 2004.
24. Martinez MN, Emfinger CH, Overton MH, Hill S, Ramaswamy TS, Cappel DA, Wu K, Fazio S, McDonald WH, Hachey DL, Tabb DL, Stafford JM. Obesity and altered glucose metabolism impact HDL composition in CETP transgenic mice: a role for ovarian hormones. J Lipid Res 53: 379-389, 2012.
25. Matic M, Bryzgalova G, Gao H, Antonson P, Humire P, Omoto Y, Portwood N, Pramfalk C, Efendic S, Berggren PO, Gustafsson JÅ, Dahlman-Wright K. Estrogen signalling and the metabolic syndrome: targeting the hepatic estrogen receptor alpha action. PLoS One 8: e57458, 2013.
26. Matthews KA, Meilahn E, Kuller LH, Kelsey SF, Caggiula AW, Wing RR. Menopause and risk factors for coronary heart disease. N Engl J Med 321: 641-646, 1989.
27. Meegalla RL, Billheimer JT, Cheng D. Concerted elevation of acylcoenzyme A:diacylglycerol acyltransferase (DGAT) activity through independent stimulation of mRNA expression of DGAT1 and DGAT2 by carbohydrate and insulin. Biochem Biophys Res Commun 298: 317-323, 2002.
28. Ohlsson C, Hellberg N, Parini P, Vidal O, Bohlooly YM, Rudling M, Lindberg MK, Warner M, Angelin B, Gustafsson JA. Obesity and disturbed lipoprotein profile in estrogen receptor-alpha-deficient male mice. Biochem Biophys Res Commun 278: 640-645, 2000.
29. Peter I, Huggins GS, Shearman AM, Pollak A, Schmid CH, Cupples LA, Demissie S, Patten RD, Karas RH, Housman DE, Mendelsohn ME, Vasan RS, Benjamin EJ. Age-related changes in echocardiographic measurements: association with variation in the estrogen receptor-alpha gene. Hypertension 49: 1000-1006, 2007.
30. Pitteloud N, Mootha VK, Dwyer AA, Hardin M, Lee H, Eriksson KF, Tripathy DJ, Yialamas M, Groop L, Elahi D, Hayes FJ. Relationship between testosterone levels, insulin sensitivity, and mitochondrial function in men. Diabetes Care 28: 1636-1642, 2005.
31. Raabe M, Véniant MM, Sullivan MA, Zlot CH, Björkegren J, Nielsen LB, Wong JS, Hamilton RL, Young SG. Analysis of the role of microsomal triglyceride transfer protein in the liver of tissue-specific knockout mice. J Clin Invest 103: 1287-1298, 1999.
32. Rhee EP, Cheng S, Larson MG, Walford GA, Lewis GD, McCabe E, Yang E, Farrell L, Fox CS, O'Donnell CJ, Carr SA, Vasan RS, Florez JC, Clish CB, Wang TJ, Gerszten RE. Lipid profiling identifies a triacylglycerol signature of insulin resistance and improves diabetes prediction in humans. J Clin Invest 121: 1402-1411, 2011.
33. Ribas V, Nguyen MT, Henstridge DC, Nguyen AK, Beaven SW, Watt MJ, Hevener AL. Impaired oxidative metabolism and inflammation are associated with insulin resistance in ERα-deficient mice. Am J Physiol Endocrinol Metab 298: E304-E319, 2010.
34. Rochira V, Madeo B, Zirilli L, Caffagni G, Maffei L, Carani C. Oestradiol replacement treatment and glucose homeostasis in two men with congenital aromatase deficiency: evidence for a role of oestradiol and sex steroids imbalance on insulin sensitivity in men. Diabet Med 24: 1491-1495, 2007.
35. Sato K, Iemitsu M, Aizawa K, Ajisaka R. Testosterone and DHEA activate the glucose metabolism-related signaling pathway in skeletal muscle. Am J Physiol Endocrinol Metab 294: E961-E968, 2008.
36. Schindhelm RK, Dekker JM, Nijpels G, Bouter LM, Stehouwer CD, Heine RJ, Diamant M. Alanine aminotransferase predicts coronary heart disease events: a 10-year follow-up of the Hoorn Study. Atherosclerosis 191: 391-396, 2007.
37. Smith EP, Boyd J, Frank GR, Takahashi H, Cohen RM, Specker B, Williams TC, Lubahn DB, Korach KS. Estrogen resistance caused by a mutation in the estrogen-receptor gene in a man. N Engl J Med 331: 1056-1061, 1994.
38. Steele R, Wall JS, De Bodo RC, Altszuler N. Measurement of size and turnover rate of body glucose pool by the isotope dilution method. Am J Physiol 187: 15-24, 1956.
39. Stone SJ, Myers HM, Watkins SM, Brown BE, Feingold KR, Elias PM, Farese RV Jr. Lipopenia and skin barrier abnormalities in DGAT2-deficient mice. J Biol Chem 279: 11767-11776, 2004.
40. Sung KC, Wild SH, Kwag HJ, Byrne CD. Fatty liver, insulin resistance, and features of metabolic syndrome: relationships with coronary artery calcium in 10,153 people. Diabetes Care 35: 2359-2364, 2012.
41. Swift LL, Kakkad B, Boone C, Jovanovska A, Jerome WG, Mohler PJ, Ong DE. Microsomal triglyceride transfer protein expression in adipocytes: a new component in fat metabolism. FEBS Lett 579: 3183-3189, 2005.
42. Villa A, Della Torre S, Stell A, Cook J, Brown M, Maggi A. Tetradian oscillation of estrogen receptor β is necessary to prevent liver lipid deposition. Proc Natl Acad Sci USA 109: 11806-11811, 2012.
43. Vozarova B, Stefan N, Lindsay RS, Saremi A, Pratley RE, Bogardus C, Tataranni PA. High alanine aminotransferase is associated with decreased hepatic insulin sensitivity and predicts the development of type 2 diabetes. Diabetes 51: 1889-1895, 2002.
44. Wang TJ, Larson MG, Vasan RS, Cheng S, Rhee EP, McCabe E, Lewis GD, Fox CS, Jacques PF, Fernandez C, O'Donnell CJ, Carr SA, Mootha VK, Florez JC, Souza A, Melander O, Clish CB, Gerszten RE. Metabolite profiles and the risk of developing diabetes. Nat Med 17: 448-453, 2011.
45. Woodard GA, Brooks MM, Barinas-Mitchell E, Mackey RH, Matthews KA, Sutton-Tyrrell K. Lipids, menopause, and early atherosclerosis in Study of Women's Health Across the Nation Heart women. Menopause 18: 376-384, 2011.
46. Wu K, Cappel D, Martinez M, Stafford JM. Impaired-inactivation of FoxO1 contributes to glucose-mediated increases in serum very lowdensity lipoprotein. Endocrinology 151: 3566-3576, 2010.
47. Yamaguchi K, Yang L, McCall S, Huang J, Yu XX, Pandey SK, Bhanot S, Monia BP, Li YX, Diehl AM. Inhibiting triglyceride synthesis improves hepatic steatosis but exacerbates liver damage and fibrosis in obese mice with nonalcoholic steatohepatitis. Hepatology 45: 1366-1374, 2007.
48. Yen CL, Stone SJ, Koliwad S, Harris C, Farese RV Jr. Thematic review series: glycerolipids. DGAT enzymes and triacylglycerol biosynthesis. J Lipid Res 49: 2283-2301, 2008.
49. Zhu L, Brown WC, Cai Q, Krust A, Chambon P, McGuinness OP, Stafford JM. Estrogen treatment after ovariectomy protects against fatty liver and may improve pathway-selective insulin resistance. Diabetes 62: 424-434, 2013.
50. Zhu L, Johnson C, Bakovic M. Stimulation of the human CTP:phosphoethanolamine cytidylyltransferase gene by early growth response protein 1. J Lipid Res 49: 2197-2211, 2008.