A dual sugar challenge test for lipogenic sensitivity to dietary fructose.
BACKGROUND
Increased hepatic de novo lipogenesis (DNL) in response to dietary sugar is implicated in dyslipidemia, fatty liver, and insulin resistance.


OBJECTIVE
The aim of the study was to develop a simple outpatient tolerance test for lipogenic sensitivity to dietary sugar.


METHODS
In inpatients given repeated doses of fructose, protocol 1 compared the acute increase in DNL determined from the percentage of palmitate ("new palmitate") and the percentage of isotopically labeled palmitate ("%DNL") in very low-density lipoprotein triglyceride (TG). Protocol 2 compared the increase in new palmitate in outpatients given three different sugar beverages in a randomized crossover design.


METHODS
There were 15 lean and overweight volunteers in protocol 1 and 15 overweight volunteers in protocol 2.


METHODS
In protocol 1, subjects received 1.4 g/kg fructose in divided oral doses over 6 h; in protocol 2, subjects received 0.5 g/kg fructose, 0.5 g/kg fructose plus 0.5 g/kg glucose, or 1 g/kg fructose plus 1 g/kg glucose each as a single oral bolus.


METHODS
We measured the increase in DNL by two methods.


RESULTS
After repeated doses of fructose, new palmitate was significantly correlated with the increase in %DNL (Δ, r = 0.814; P < 0.001) and with fasting insulin levels (area under the curve, r = 0.754; P = 0.001). After a single sugar dose, new palmitate showed a dose effect and was greater after fructose plus glucose. Very low-density lipoprotein TG and total TG significantly increased in both protocols.


CONCLUSIONS
A single oral bolus of fructose and glucose rapidly increases serum TG and TG palmitate in overweight subjects. A dual sugar challenge test could prove useful to identify individuals at risk for carbohydrate-induced dyslipidemia and other adverse effects of increased DNL.
The Rogosin Institute, New York, New York 10065, USA. lih2013@nyp.org
Lisa C
LC
Hudgins
Thomas S
TS
Parker
Daniel M
DM
Levine
Marc K
MK
Hellerstein
D000273:Adipose Tissue / Q000033:anatomy & histology; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D018592:Cross-Over Studies; D004032:Diet; D004040:Dietary Carbohydrates / Q000494:pharmacology*; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D005632:Fructose / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007553:Isotope Labeling; D050356:Lipid Metabolism / Q000187:drug effects*; D008079:Lipoproteins, VLDL / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D050177:Overweight / Q000378:metabolism; D010168:Palmitates / Q000097:blood; D014280:Triglycerides / Q000097:blood; D055815:Young Adult
D001786:Blood Glucose; D004040:Dietary Carbohydrates; D005227:Fatty Acids; D008079:Lipoproteins, VLDL; D010168:Palmitates; D014280:Triglycerides; D005632:Fructose; D005947:Glucose
Gastroenterology. 1983 Jan;84(1):26-9
6847852
J Clin Endocrinol Metab. 2000 Dec;85(12):4515-9
11134101
Metabolism. 2005 Sep;54(9):1189-201
16125531
J Lipid Res. 2000 Apr;41(4):595-604
10744780
Am J Clin Nutr. 2008 May;87(5):1194-203
18469239
Am J Public Health. 2007 Apr;97(4):667-75
17329656
Arch Dis Child. 1984 Aug;59(8):735-8
6476870
Proc Natl Acad Sci U S A. 2007 Jul 31;104(31):12587-94
17640906
Am J Clin Nutr. 2008 Dec;88(6):1722S-1732S
19064537
Circulation. 2009 Sep 15;120(11):1011-20
19704096
Am J Clin Nutr. 2000 Feb;71(2):412-33
10648253
Am J Clin Nutr. 1988 Dec;48(6):1424-30
3202090
J Lipid Res. 2006 Aug;47(8):1651-60
16741290
Am J Gastroenterol. 2003 Jun;98(6):1348-53
12818280
Am J Clin Nutr. 2007 Jun;85(6):1511-20
17556686
J Clin Invest. 2005 May;115(5):1343-51
15864352
J Nutr. 2008 Jun;138(6):1039-46
18492831
J Lipid Res. 1998 Jun;39(6):1280-6
9643360
Curr Opin Lipidol. 2008 Feb;19(1):16-24
18196982
Gut. 1986 Oct;27(10):1161-8
3781328
Am J Clin Nutr. 2007 Oct;86(4):899-906
17921363
Curr Opin Lipidol. 2010 Feb;21(1):51-7
19956074
J Clin Invest. 1996 May 1;97(9):2081-91
8621798
Am J Clin Nutr. 1998 Apr;67(4):631-9
9537610