Fructose induced lipogenesis: from sugar to fat to insulin resistance.
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.
Departments of Internal Medicine, Yale University School of Medicine, New Haven, CT 06536-8012, USA. varman.samuel@yale.edu
Varman T
VT
Samuel
D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology; D004040:Dietary Carbohydrates / Q000008:administration & dosage / Q000009:adverse effects; D004789:Enzyme Activation / Q000187:drug effects; D005234:Fatty Liver / Q000209:etiology; D005632:Fructose / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D006801:Humans; D007333:Insulin Resistance; D050155:Lipogenesis / Q000187:drug effects*; D051379:Mice; D065626:Non-alcoholic Fatty Liver Disease; D009765:Obesity / Q000209:etiology; D047495:PPAR gamma / Q000494:pharmacology; D020033:Protein Isoforms; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism; D000071701:Regulatory Factor X Transcription Factors; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects
D004268:DNA-Binding Proteins; D004040:Dietary Carbohydrates; D047495:PPAR gamma; D020033:Protein Isoforms; D011768:Pyruvate Dehydrogenase Complex; D000071701:Regulatory Factor X Transcription Factors; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors; D005632:Fructose