High-fat diet and glucocorticoid treatment cause hyperglycemia associated with adiponectin receptor alterations.
BACKGROUND
Adiponectin is the most abundant plasma protein synthesized for the most part in adipose tissue, and it is an insulin-sensitive hormone, playing a central role in glucose and lipid metabolism. In addition, it increases fatty acid oxidation in the muscle and potentiates insulin inhibition of hepatic gluconeogenesis. Two adiponectin receptors have been identified: AdipoR1 is the major receptor expressed in skeletal muscle, whereas AdipoR2 is mainly expressed in liver. Consumption of high levels of dietary fat is thought to be a major factor in the promotion of obesity and insulin resistance. Excessive levels of cortisol are characterized by the symptoms of abdominal obesity, hypertension, glucose intolerance or diabetes and dyslipidemia; of note, all of these features are shared by the condition of insulin resistance. Although it has been shown that glucocorticoids inhibit adiponectin expression in vitro and in vivo, little is known about the regulation of adiponectin receptors. The link between glucocorticoids and insulin resistance may involve the adiponectin receptors and adrenalectomy might play a role not only in regulate expression and secretion of adiponectin, as well regulate the respective receptors in several tissues.


RESULTS
Feeding of a high-fat diet increased serum glucose levels and decreased adiponectin and adipoR2 mRNA expression in subcutaneous and retroperitoneal adipose tissues, respectively. Moreover, it increased both adipoR1 and adipoR2 mRNA levels in muscle and adipoR2 protein levels in liver. Adrenalectomy combined with the synthetic glucocorticoid dexamethasone treatment resulted in increased glucose and insulin levels, decreased serum adiponectin levels, reduced adiponectin mRNA in epididymal adipose tissue, reduction of adipoR2 mRNA by 7-fold in muscle and reduced adipoR1 and adipoR2 protein levels in muscle. Adrenalectomy alone increased adiponectin mRNA expression 3-fold in subcutaneous adipose tissue and reduced adipoR2 mRNA expression 2-fold in liver.


CONCLUSIONS
Hyperglycemia as a result of a high-fat diet is associated with an increase in the expression of the adiponectin receptors in muscle. An excess of glucocorticoids, rather than their absence, increase glucose and insulin and decrease adiponectin levels.
Disciplina de Fisiologia da Nutrição, Departamento de Fisiologia, Universidade Federal de São Paulo, São Paulo, Brasil.
Cristiane
C
de Oliveira
Ana B M
AB
de Mattos
Carolina
C
Biz
Lila M
LM
Oyama
Eliane B
EB
Ribeiro
Cláudia Maria Oller
CM
do Nascimento
D052242:Adiponectin / Q000235:genetics / Q000378:metabolism*; D000273:Adipose Tissue / Q000378:metabolism; D000315:Adrenalectomy; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003345:Corticosterone / Q000097:blood; D003907:Dexamethasone / Q000009:adverse effects*; D004041:Dietary Fats / Q000008:administration & dosage*; D015536:Down-Regulation; D005938:Glucocorticoids / Q000009:adverse effects*; D006943:Hyperglycemia / Q000209:etiology / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D054419:Receptors, Adiponectin / Q000235:genetics / Q000378:metabolism*
D052242:Adiponectin; D001786:Blood Glucose; D004041:Dietary Fats; D005938:Glucocorticoids; D007328:Insulin; D054419:Receptors, Adiponectin; D003907:Dexamethasone; D003345:Corticosterone
FEBS Lett. 2001 Oct 26;507(2):142-6
11684087
Metabolism. 2006 Mar;55(3):396-401
16483885
Biochem J. 1986 Oct 1;239(1):233-6
3099779
Biochem Biophys Res Commun. 2002 Jan 25;290(3):1084-9
11798186
Diabetes. 2004 Jul;53(7):1790-7
15220203
Proc Jpn Acad Ser B Phys Biol Sci. 2010;86(2):131-41
20154470
Diabetes. 2004 Sep;53(9):2195-201
15331527
J Clin Endocrinol Metab. 2001 May;86(5):1930-5
11344187
J Allergy Clin Immunol. 2000 Oct;106(4):651-9
11031335
Biochem Pharmacol. 2005 Jul 15;70(2):249-57
15904896
Pflugers Arch. 2008 Jan;455(4):701-9
17717684
Diabetologia. 2004 May;47(5):917-25
15127202
Am J Physiol Endocrinol Metab. 2007 Apr;292(4):E1079-86
17164441
Am J Physiol Heart Circ Physiol. 2006 Jun;290(6):H2409-16
16415076
Horm Metab Res. 2002 Nov-Dec;34(11-12):650-4
12660876
Am J Med. 2002 Dec 30;113 Suppl 9B:13S-24S
12566134
Am J Physiol Regul Integr Comp Physiol. 2010 Aug;299(2):R500-8
20554937
Int J Exp Diabetes Res. 2000;1(2):81-8
11469400
Am J Physiol Endocrinol Metab. 2005 May;288(5):E876-82
15613685
Metabolism. 2011 Mar;60(3):430-7
20423746
Am J Physiol Endocrinol Metab. 2010 Sep;299(3):E506-15
20570822
Endocrine. 2005 Feb;26(1):65-9
15805587
Nature. 2003 Jun 12;423(6941):762-9
12802337
Diabetologia. 2006 Jun;49(6):1303-10
16609881
J Negat Results Biomed. 2006 Sep 11;5:14
16965635
Clin Dermatol. 1986 Jan-Mar;4(1):161-9
2978681
Horm Metab Res. 1986 May;18(5):296-8
3522389
Steroids. 2008 Oct;73(11):1128-36
18534650
Eur J Pharmacol. 2007 Aug 13;569(1-2):155-62
17574233
Biochem Biophys Res Commun. 2009 Dec 25;390(4):1208-13
19878661
Biochem J. 1976 Nov 15;160(2):413-6
12755
Biochem Biophys Res Commun. 2003 Dec 26;312(4):1118-22
14651988
J Biol Chem. 2004 Jul 16;279(29):30817-22
15123605
Eur J Endocrinol. 2003 Mar;148(3):293-300
12611609
Int J Mol Med. 2006 Jun;17(6):975-80
16685404
Eur J Pharmacol. 2005 Jul 25;518(1):71-6
15979609
Diabetes. 1995 Apr;44(4):441-5
7698514
Am J Physiol Endocrinol Metab. 2002 Dec;283(6):E1266-71
12388167
Diabetes. 2002 Jul;51(7):2113-8
12086940
Obesity (Silver Spring). 2006 Jan;14(1):28-35
16493120
Endocrinology. 2005 Feb;146(2):913-9
15550507
Biochem Biophys Res Commun. 2001 Nov 16;288(5):1102-7
11700024
Clin Sci (Lond). 2003 Oct;105(4):403-8
12780342
Diabetologia. 2001 Jul;44(7):805-17
11508264
Obes Res. 2005 Apr;13(4):662-9
15897474
Obesity (Silver Spring). 2006 Dec;14(12):2145-53
17189540
Endocrinology. 2005 Mar;146(3):1576-87
15591151
Mol Cell Endocrinol. 2004 Apr 30;219(1-2):9-15
15149722
Clin Endocrinol (Oxf). 2008 Nov;69(5):745-50
18363889
Am J Physiol. 1997 Dec;273(6):E1168-77
9435533
Life Sci. 2003 Aug 1;73(11):1369-81
12850498
Nat Med. 2002 Nov;8(11):1288-95
12368907
Arterioscler Thromb Vasc Biol. 2000 Jun;20(6):1595-9
10845877
Methods. 2001 Dec;25(4):402-8
11846609
J Clin Invest. 2001 Dec;108(12):1875-81
11748271
Inflammation. 2003 Feb;27(1):1-7
12772772
Diabetes Metab. 2008 Feb;34(1):12-8
18069030
Circulation. 2001 Feb 27;103(8):1057-63
11222466
Obes Res. 2005 Feb;13(2):306-11
15800288
Diabetes. 1997 Feb;46(2):209-14
9000696
J Am Coll Nutr. 2001 Oct;20(5):529-36
11601568
Endocrinology. 2007 Feb;148(2):683-92
17068142
J Gastrointest Surg. 2009 Nov;13(11):2043-9
19763702
J Biol Chem. 1951 Nov;193(1):265-75
14907713
Hypertension. 2003 Jul;42(1):76-81
12796280
FEBS Lett. 2004 Jan 30;558(1-3):27-32
14759511
Obes Rev. 2005 Feb;6(1):13-21
15655035
J Endocrinol. 1996 Mar;148(3):391-8
8778217
J Clin Endocrinol Metab. 2002 Oct;87(10):4652-6
12364452