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Fructose overconsumption causes dyslipidemia and ectopic lipid deposition in healthy subjects with and without a family history of type 2 diabetes^1,2,3,4

¹ From the Department of Physiology, University of Lausanne, Lausanne, Switzerland (K-AL, DF, MB, CT, and LT); the Department of Clinical Research, MR Spectroscopy and Methodology, University of Bern, Bern, Switzerland (MI, RK, and CB); and the Division of Diabetes, Endocrinology and Metabolism, Lausanne University Hospital, Lausanne, Switzerland (LT).

² Presented as an abstract at the 68th annual meeting of the American Diabetes Association, San Francisco, CA, June 2008 [Diabetes 2008;5(suppl 1):A11].

³ Supported by grants 310000-109737/1 (to LT) and 310000-118219 (to CB) from the Swiss National Science Foundation and by grants from the Novartis Foundation (to LT and K-AL) and Takeda (K-AL).

⁴ Address correspondence to L Tappy, Faculty of Biology and Medicine, Department of Physiology, Rue du Bugnon 7, CH-1005 Lausanne, Switzerland. E-mail: luc.tappy{at}unil.ch.

ABSTRACT

Background: Both nutritional and genetic factors are involved in the pathogenesis of nonalcoholic fatty liver disease and insulin resistance.

Objective: The aim was to assess the effects of fructose, a potent stimulator of hepatic de novo lipogenesis, on intrahepatocellular lipids (IHCLs) and insulin sensitivity in healthy offspring of patients with type 2 diabetes (OffT2D)—a subgroup of individuals prone to metabolic disorders.

Design: Sixteen male OffT2D and 8 control subjects were studied in a crossover design after either a 7-d isocaloric diet or a hypercaloric high-fructose diet (3.5 g · kg FFM^–1 · d^–1, +35% energy intake). Hepatic and whole-body insulin sensitivity were assessed with a 2-step hyperinsulinemic euglycemic clamp (0.3 and 1.0 mU · kg^–1 · min^–1), together with 6,6-[²H₂]glucose. IHCLs and intramyocellular lipids (IMCLs) were measured by ¹H-magnetic resonance spectroscopy.

Results: The OffT2D group had significantly (P < 0.05) higher IHCLs (+94%), total triacylglycerols (+35%), and lower whole-body insulin sensitivity (–27%) than did the control group. The high-fructose diet significantly increased IHCLs (control: +76%; OffT2D: +79%), IMCLs (control: +47%; OffT2D: +24%), VLDL-triacylglycerols (control: +51%; OffT2D: +110%), and fasting hepatic glucose output (control: +4%; OffT2D: +5%). Furthermore, the effects of fructose on VLDL-triacylglycerols were higher in the OffT2D group (group x diet interaction: P < 0.05).

Conclusions: A 7-d high-fructose diet increased ectopic lipid deposition in liver and muscle, and fasting VLDL-triacylglycerols and decreased hepatic insulin sensitivity. Fructose-induced alterations in VLDL-triacylglycerols appeared to be of greater magnitude in the OffT2D group, which suggests that these individuals may be more prone to developing dyslipidemia when challenged by high fructose intakes. This trial was registered at clinical trials.gov as NCT00523562.

Received for publication December 10, 2008. Accepted for publication March 30, 2009.

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				L. Tappy and K.-A. Le Metabolic Effects of Fructose and the Worldwide Increase in Obesity Physiol Rev, January 1, 2010; 90(1): 23 - 46. [Abstract] [Full Text] [PDF]