Increased whole-body adiposity without a concomitant increase in liver fat is not associated with augmented metabolic dysfunction.
Aim of this study was to determine whether an increase in adiposity, without a concomitant increase in intrahepatic triglyceride (IHTG) content, is associated with a deterioration in metabolic function. To this end, multiorgan insulin sensitivity, assessed by using a two-stage hyperinsulinemic-euglycemic clamp procedure in conjunction with stable isotopically labeled tracer infusion, and very low-density lipoprotein (VLDL) kinetics, assessed by using stable isotopically labeled tracer infusion and mathematical modeling, were determined in 10 subjects with class I obesity (BMI: 31.6 +/- 0.3 kg/m(2); 37 +/- 2% body fat; visceral adipose tissue (VAT): 1,225 +/- 144 cm(3)) and 10 subjects with class III obesity (BMI: 41.5 +/- 0.5 kg/m(2); 43 +/- 2% body fat; VAT: 2,121 +/- 378 cm(3)), matched on age, sex, and IHTG content (14 +/- 4 and 14 +/- 3%, respectively). No differences between class I and class III obese groups were detected in insulin-mediated suppression of palmitate (67 +/- 3 and 65 +/- 3%, respectively; P = 0.635) and glucose (67 +/- 3 and 73 +/- 5%, respectively; P = 0.348) rates of appearance in plasma, and the insulin-mediated increase in glucose disposal (218 +/- 18 and 193 +/- 30%, respectively; P = 0.489). In addition, no differences between class I and class III obese groups were detected in secretion rates of VLDL-triglyceride (6.5 +/- 1.0 and 6.0 +/- 1.4 micromol/l x min, respectively; P = 0.787) and VLDL-apolipoprotein B-100 (0.40 +/- 0.05 and 0.41 +/- 0.04 nmol/l x min, respectively; P = 0.866), and plasma clearance rates of VLDL-triglyceride (31 (16-59) and 29 (18-46) ml/min, respectively; P = 0.888) and VLDL-apolipoprotein B-100 (15 (11-19) and 17 (11-25) ml/min, respectively; P = 0.608). We conclude that increased adiposity without a concomitant increase in IHTG content does not cause additional abnormalities in adipose tissue, skeletal muscle, and hepatic insulin sensitivity, or VLDL metabolism.
Magkos
Faidon
F
Division of Geriatrics and Nutritional Science, Center for Human Nutrition, Washington University School of Medicine, St Louis, Missouri, USA.
Fabbrini
Elisa
E
Mohammed
B Selma
BS
Patterson
Bruce W
BW
Klein
Samuel
S
D000328:Adult; D053299:Apolipoprotein B-100 / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism*; D015243:Cholesterol, VLDL / Q000097:blood; D005260:Female; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008962:Models, Theoretical; D009765:Obesity / Q000378:metabolism*; D010168:Palmitates / Q000097:blood; D014280:Triglycerides / Q000378:metabolism*
D053299:Apolipoprotein B-100; D001786:Blood Glucose; D015243:Cholesterol, VLDL; D007328:Insulin; D010168:Palmitates; D014280:Triglycerides
J Clin Endocrinol Metab. 2007 Apr;92(4):1311-8
17264179
Am J Physiol Endocrinol Metab. 2003 Mar;284(3):E549-56
12475754
Am J Clin Nutr. 2000 Sep;72(3):694-701
10966886
J Clin Invest. 2004 Jun;113(11):1530-2
15173878
Diabetologia. 2005 Apr;48(4):634-42
15747110
Obes Res. 1998 Sep;6 Suppl 2:51S-209S
9813653
J Cardiometab Syndr. 2007 Spring;2(2):136-8
17684473
J Clin Endocrinol Metab. 2002 Nov;87(11):5044-51
12414870
Am J Physiol Endocrinol Metab. 2005 Feb;288(2):E462-8
15339742
Gut. 2005 Jan;54(1):122-7
15591516
Proc Nutr Soc. 2009 Nov;68(4):370-7
19698203
J Lipid Res. 1988 Nov;29(11):1461-73
3241122
Arch Intern Med. 2008 Aug 11;168(15):1609-16
18695074
J Clin Invest. 1989 Jul;84(1):205-13
2661589
Nutrition. 2002 Jan;18(1):66-70
11827768
Gastroenterology. 2002 Sep;123(3):882-932
12198715
J Lipid Res. 2007 May;48(5):1204-11
17325388
Gastroenterology. 2008 Feb;134(2):424-31
18242210
Nature. 2006 Dec 14;444(7121):881-7
17167477
Am J Epidemiol. 1996 Feb 1;143(3):228-39
8561156
Am J Physiol Endocrinol Metab. 2002 Mar;282(3):E657-63
11832370
Curr Opin Lipidol. 1997 Jun;8(3):146-53
9211062
Arch Med Res. 2008 Nov;39(8):803-8
18996295
J Clin Endocrinol Metab. 2002 Jul;87(7):3023-8
12107194
Gastroenterology. 2006 May;130(6):1564-72
16697719
Clin Chem. 1972 Jun;18(6):499-502
4337382
Am J Epidemiol. 1990 Sep;132(3):501-13
2389754
J Clin Invest. 1991 Aug;88(2):609-13
1864970
Annu Rev Physiol. 2010;72:219-46
20148674
Gastroenterology. 2006 Jun;130(7):2023-30
16762625
Diabetologia. 2000 Dec;43(12):1498-506
11151758
Arterioscler Thromb Vasc Biol. 2004 May;24(5):795-7
15132969
Diabetes. 2009 Mar;58(3):693-700
19066313
Clin Lipidol. 2009 Apr 1;4(2):215-230
20161007
Diabetes Care. 1999 Sep;22(9):1462-70
10480510
Eur J Ultrasound. 2001 Dec;14(2-3):121-8
11704429
J Lipid Res. 1999 Nov;40(11):2118-24
10553015
Diabetes Care. 1998 Apr;21(4):518-24
9571335
Gastroenterology. 2005 Jul;129(1):113-21
16012941
J Lipid Res. 2002 Feb;43(2):223-33
11861664
Ann N Y Acad Sci. 1959 Sep 25;82:420-30
13833973
Epidemiol Rev. 2007;29:77-87
17478441
Diabetes Care. 2007 Mar;30(3):683-8
17327341
Diabetologia. 2006 Apr;49(4):755-65
16463046
J Clin Invest. 2004 Jun;113(11):1582-8
15173884
Am J Clin Nutr. 2008 Aug;88(2):257-62
18689359
Proc Natl Acad Sci U S A. 2009 Sep 8;106(36):15430-5
19706383
J Lipid Res. 1994 Aug;35(8):1490-6
7989873
J Clin Invest. 1997 Sep 1;100(5):1166-73
9303923
Diabetes. 2007 Apr;56(4):1010-3
17287468
Proc Natl Acad Sci U S A. 1986 Nov;83(21):8142-6
3464946
Gend Med. 2008 Dec;5(4):361-71
19108808
Am J Physiol Endocrinol Metab. 2007 Dec;293(6):E1663-9
17911339
Gastroenterology. 2008 Jul;135(1):122-30
18474251
Gastroenterology. 2008 May;134(5):1369-75
18355813