Fructose induced lipogenesis: From sugar to fat to insulin resistance

Departments of Internal Medicine, Yale University School of Medicine, New Haven, CT 06536-8012, USA.
Trends in Endocrinology and Metabolism (Impact Factor: 9.39). 11/2010; 22(2):60-5. DOI: 10.1016/j.tem.2010.10.003
Source: PubMed


Increasing consumption of sugars is one of the contributing factors to the obesity epidemic. Both cane sugar and high-fructose corn syrup contain glucose and fructose. Fructose, in contrast to glucose, is known to potently stimulate lipogenesis, but the mechanisms responsible are not yet fully known. This paper reviews several possible pathways that might be involved, such as activation of pyruvate dehydrogenase, and transcriptional activation of sterol regulatory element binding protein 1c by key regulators such as peroxisome proliferator activated receptor-γ co-activator 1β and the splice variant of X-box binding protein 1. Together, these pathways might establish a feed forward cycle that can rapidly increase hepatic lipogenesis. As a result, dietary fructose might promote the development of nonalcoholic fatty liver disease, which in and of itself, can result in hepatic insulin resistance, a key feature of type 2 diabetes mellitus.

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    • "High levels of fructose may thus act as a nonregulated source of hepatic acetyl-CoA, which is a substrate that can enter DNL [9]. In addition, a high intake of fructose seems to stimulate gene expression and activity of lipogenic enzymes in the liver [40] [41] [66] [68]. Recently, fructose has also been shown to give a higher increase in fibroblast growth factor 21 (FGF21) than glucose. "
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    ABSTRACT: A high intake of sugars has been linked to diet-induced health problems. The fructose content in sugars consumed may also affect health, although the extent to which fructose has a particularly significant negative impact on health remains controversial. The aim of this narrative review is to describe the body's fructose management and to discuss the role of fructose as a risk factor for atherosclerosis, type 2 diabetes, and obesity. Despite some positive effects of fructose, such as high relative sweetness, high thermogenic effect, and low glycaemic index, a high intake of fructose, particularly when combined with glucose, can, to a larger extent than a similar glucose intake, lead to metabolic changes in the liver. Increased de novo lipogenesis (DNL), and thus altered blood lipid profile, seems to be the most prominent change. More studies with realistic consumption levels of fructose are needed, but current literature does not indicate that a normal consumption of fructose (approximately 50-60 g/day) increases the risk of atherosclerosis, type 2 diabetes, or obesity more than consumption of other sugars. However, a high intake of fructose, particularly if combined with a high energy intake in the form of glucose/starch, may have negative health effects via DNL.
    Journal of nutrition and metabolism 07/2015; 2015:823081. DOI:10.1155/2015/823081
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    • "Only insignificant amounts of fructose enter the systemic circulation on consumption of a normal healthy diet. However, the frequent and high consumption of sugar-based beverages and food is reported to causes dyslipidemia, nonalcoholic fatty liver diseases, and other metabolic disorders (Kavanagh et al. 2013; Samuel 2011). High circulating levels of fructose overwhelms the ability of the liver to metabolize the ingested fructose completely, resulting in a spillover of fructose into the systemic circulation (Hui et al. 2009; Munstedt et al. 2011). "
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    ABSTRACT: The development of obesity is becoming an international problem and the role of fructose is unclear. Studies using liver tissue and hepatocytes have contributed to the understanding of fructose metabolism. Excess fructose consumption also affects extra hepatic tissues including adipose tissue. The effects of fructose on human adipocytes are not yet fully characterized, although in vivo studies have noted increased adiposity and weight gain in response to fructose sweetened-beverages. In order to understand and predict the metabolic responses of adipocytes to fructose, this study examined differentiating and differentiated human adipocytes in culture, exposed to a range of fructose concentrations equivalent to that reported in blood after consuming fructose. A stable isotope based dynamic profiling method using [U-13C6]-D-fructose tracer was used to examine the metabolism and fate of fructose. A targeted stable isotope tracer fate association method was used to analyze metabolic fluxes and flux surrogates with exposure to escalating fructose concentration. This study demonstrated that fructose stimulates anabolic processes in adipocytes robustly, including glutamate and de novo fatty acid synthesis. Furthermore, fructose also augments the release of free palmitate from fully differentiated adipocytes. These results imply that in the presence of fructose, the metabolic response of adipocytes in culture is altered in a dose dependent manner, particularly favoring increased glutamate and fatty acid synthesis and release, warranting further in vivo studies.
    Metabolomics 06/2015; DOI:10.1007/s11306-014-0716-0 · 3.86 Impact Factor
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    • "Excessive food ingestion and the increase in consumption of a high-fat and high-fructose diet (HFF) have been related to the increase in obesity, glucose intolerance, insulin resistance (IR), and type 2 diabetes in humans [1] [2]. HFF may cause problems in controlling glycemia, insulin signaling, and glucose transport. "
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    ABSTRACT: Objective: The aim of this study was to investigate the effects of chia seed and chia oil on heat shock protein (HSP) and related parameters in diet-induced obese rats. Methods: Animals were divided in six groups: control, high-fat and high-fructose diet (HFF), and HFF with chia seed or chia oil in short (6-wk) and long (12-wk) treatments. Plasma indicators of glucose tolerance and liver damage, skeletal muscle expression of antioxidant enzymes, and proteins controlling oxidative energy metabolism were determined. The limit of significance was set at P < 0.05. Results: The HFF diet induced glucose intolerance, insulin resistance, oxidative stress, and altered parameters related to obesity complications. The consumption of chia seed or chia oil did not reduce body weight gain or abdominal fat accumulation. However, chia seed and chia oil in both treatments improved glucose and insulin tolerance. Chia oil in both treatments induced expression of HSP70 and HSP25 in skeletal muscle. Short treatment with chia seed increased expression of HSP70, but not HSP25. Chia oil in both treatments restored superoxide dismutase and glutathione peroxidase expression. Extended treatment with chia seed and short treatment with chia oil restored peroxisome proliferator-activated receptor-g coactivator-1a (PGC-1a) expression. Conclusion: Chia oil restored the antioxidant system and induced the expression of a higher number of proteins than chia seed. The present study demonstrated new properties and molecular mechanisms associated with the beneficial effects of chia seed and chia oil consumption in diet-induced obese rats.
    Nutrition 05/2015; 31(5):740-748. · 2.93 Impact Factor
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