Effect of a High-Fructose Weight-Maintaining Diet on Lipogenesis and Liver Fat

Schwarz, Jean-Marc; Noworolski, Susan M.; Wen, Ming; Dyachenko, Artem; Prior, Jessica L.; Weinberg, Melissa E.; Herraiz, Laurie A.; Tai, Viva; Bergeron, Nathalie; Bersot, Thomas P.; Rao, Madhu N.; Schambelan, Morris; Mulligan, Kathleen

doi:10.1210/jc.2014-3678

Cited by 192 publications

(195 citation statements)

References 39 publications

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“…We have recently shown that in healthy adults fed isocaloric diets, DNL and liver fat were higher during high-fructose feeding, when compared with low-fructose feeding. 18 Those results, taken together with those of the present study, support the hypothesis that DNL is an important mechanism in the modulation of liver fat. 8, 3542 Moreover, the increases in VAT with high-fructose feeding 2 and the decrease in VAT observed with fructose restriction observed in the present study suggest primary links between fructose consumption, DNL, and ectopic fat.…”

Section: Discussionsupporting

confidence: 90%

“…We recently demonstrated that in weight-stable healthy men, high fructose intake for a 9-day period was associated with higher DNL and liver fat, compared with a diet with identical energy and macronutrient intake, but in which complex carbohydrate (starch) was substituted for sugar. 18 Thus we provided evidence linking fructose-driven DNL with liver fat and demonstrated that short-term reduction in fructose intake was consistently associated with lower levels of liver fat and rates of DNL, even in the absence of weight loss.…”

Section: Introductionmentioning

confidence: 66%

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Effects of Dietary Fructose Restriction on Liver Fat, De Novo Lipogenesis, and Insulin Kinetics in Children With Obesity

et al. 2017

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Background & Aims Consumption of sugar is associated with obesity, type 2 diabetes mellitus, non-alcoholic fatty liver disease, and cardiovascular disease. The conversion of fructose to fat in liver (de novo lipogenesis, DNL) may be a modifiable pathogenetic pathway. We determined the effect of 9 days of isocaloric fructose restriction on DNL, liver fat, visceral fat (VAT), subcutaneous fat, and insulin kinetics in obese Latino and African American children with habitual high sugar consumption (fructose intake more than 50 g/day). Methods Children (9–18 years old; n = 41) had all meals provided for 9 days with the same energy and macronutrient composition as their standard diet, but with starch substituted for sugar, yielding a final fructose content of 4% of total kcal. Metabolic assessments were performed before and after fructose restriction. Liver fat, VAT, and subcutaneous fat were determined by magnetic resonance spectroscopy and imaging. The fractional DNL area under the curve value was measured using stable isotope tracers and gas chromatography/mass spectrometry. Insulin kinetics were calculated from oral glucose tolerance tests. Paired analyses compared change from day 0 to day 10 within each child. Results Compared with baseline, on day 10, liver fat decreased from a median of 7.2% (inter-quartile range, 2.5%–14.8%) to 3.8% (inter-quartile range, 1.7%–15.5%)(P<.001) and VAT decreased from 123 cm3 (inter-quartile range, 85–145 cm3) to 110 cm3 (inter-quartile range, 84–134 cm3) (P<.001). The DNL area under the curve decreased from 68% (inter-quartile range, 46%–83%) to 26% (inter-quartile range, 16%–37%) (P<0.001). Insulin kinetics improved (P<.001). These changes occurred irrespective of baseline liver fat. Conclusions Short-term (9 day) isocaloric fructose restriction decreased liver fat, VAT, and DNL, and improved insulin kinetics in children with obesity. These findings support efforts to reduce sugar consumption. ClinicalTrials.gov no: NCT01200043

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 66%

Effects of Dietary Fructose Restriction on Liver Fat, De Novo Lipogenesis, and Insulin Kinetics in Children With Obesity

et al. 2017

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“…85 Markedly reducing intake of added sugars, especially sucrose and HFCS, can lead to NAFLD regression and, presumably, reduction of associated CHD risk. 87, 88 …”

Section: Sugar and Chd Risk Factorsmentioning

confidence: 99%

The Evidence for Saturated Fat and for Sugar Related to Coronary Heart Disease

DiNicolantonio

Lucan

O’Keefe

2016

Progress in Cardiovascular Diseases

284

143

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Dietary guidelines continue to recommend restricting intake of saturated fats. This recommendation follows largely from the observation that saturated fats can raise levels of total serum cholesterol (TC), thereby putatively increasing the risk of atherosclerotic coronary heart disease (CHD). However, TC is only modestly associated with CHD, and more important than the total level of cholesterol in the blood may be the number and size of low-density lipoprotein (LDL) particles that contain it. As for saturated fats, these fats are a diverse class of compounds; different fats may have different effects on LDL and on broader CHD risk based on the specific saturated fatty acids (SFAs) they contain. Importantly, though, people eat foods, not isolated fatty acids. Some food sources of SFAs may pose no risk for CHD or possibly even be protective. Thus, advice to reduce saturated fat in the diet without regard to such nuance could actually increase people’s risk of CHD. When saturated fats are replaced with refined carbohydrates, and specifically with added sugars (like sucrose or high fructose corn syrup), the end result is not favorable for heart health. Such replacement leads to changes in LDL, high-density lipoprotein (HDL), and triglycerides that may increase the risk of CHD. Additionally, diets high in sugar may induce many other abnormalities associated with elevated CHD risk, including elevated levels of glucose, insulin, and uric acid, impaired glucose tolerance, insulin and leptin resistance, non-alcoholic fatty liver disease, and altered platelet function. A diet high in added sugars has been found to cause a 3-fold increased risk of death due to cardiovascular disease. But sugars, like saturated fats, are a diverse class of compounds. The monosaccharide, fructose, and fructose-containing sweeteners (e.g., sucrose) result in greater degrees of metabolic abnormalities than seen with glucose (either isolated as a monomer or in chains as starch) and may present greater risk for CHD. This paper reviews the evidence linking saturated fats and sugars to CHD, and concludes that the latter is more of a problem than the former. Dietary guidelines should shift focus away from reducing saturated fat, and from replacing saturated fat with carbohydrates, specifically when these carbohydrates are refined. To reduce the burden of CHD, guidelines should focus particularly on reducing intake of concentrated sugars, specifically the fructose-containing sugars like sucrose and high-fructose corn syrup in the form of ultra-processed foods and beverages.

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“…Schwarz et al demonstrated that de novo lipogenesis was ~60% higher in healthy men fed an isocaloric, high-fructose diet (25% calories) for nine days relative to when the subjects ate a complex carbohydrate diet [9]. Le et al compared normoglycemic, lean, insulin sensitive individuals with normoglycemic and lean, but insulin resistant offspring of patients with T2DM before and after 7 days of a hypercaloric diet in which an additional 35% of their calories were derived from fructose [10].…”

Section: High Fructose Consumption Rapidly Impacts Metabolismmentioning

confidence: 99%

The Sweet Path to Metabolic Demise: Fructose and Lipid Synthesis

Herman

Samuel

2016

Trends in Endocrinology & Metabolism

190

143

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Epidemiological studies link fructose consumption with metabolic disease, an association attributable in part to fructose mediated lipogenesis. The mechanisms governing fructose-induced lipogenesis and disease remain debated. Acutely, fructose increases de novo lipogenesis through the efficient and uninhibited action of Ketohexokinase and Aldolase B, which yields substrates for fatty-acid synthesis. Chronic fructose consumption further enhances the capacity for hepatic fructose metabolism via activation of several key transcription factors (i.e. SREBP1c and ChREBP), which augment expression of lipogenic enzymes, increasing lipogenesis, further compounding hypertriglyceridemia, and hepatic steatosis. Hepatic insulin resistance develops from diacylglycerol-PKCε mediated impairment of insulin signaling and possibly additional mechanisms. Initiatives that decrease fructose consumption and therapies that block fructose mediated lipogenesis are needed to avert future metabolic pandemics.

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Effect of a High-Fructose Weight-Maintaining Diet on Lipogenesis and Liver Fat

Abstract: Short-term high-fructose intake was associated with increased DNL and liver fat in healthy men fed weight-maintaining diets.

Cited by 192 publications

References 39 publications

Effects of Dietary Fructose Restriction on Liver Fat, De Novo Lipogenesis, and Insulin Kinetics in Children With Obesity

Effects of Dietary Fructose Restriction on Liver Fat, De Novo Lipogenesis, and Insulin Kinetics in Children With Obesity

The Evidence for Saturated Fat and for Sugar Related to Coronary Heart Disease

The Sweet Path to Metabolic Demise: Fructose and Lipid Synthesis

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