The good, the bad, and the unknown: Fructose and FGF21.
The good, the bad, and the unknown: Fructose and FGF21.
复制标题
好的、坏的和未知的：果糖和 FGF21。
DOI：
10.1016/j.molmet.2014.11.002
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发表时间：
2015
影响因子：
8.1
通讯作者：
Havel,PeterJ
中科院分区：
文献类型：
--
作者：
Hofmann,SusannaM;Havel,PeterJ
In this issue of Molecular Metabolism, Dushay et al. report new results demonstrating fructose ingestion in humans acutely and robustly raises circulating levels of fibroblast growth factor 21 (FGF21)[1], a recently discovered hormone that has been proposed to have beneficial effects on metabolic health, including reduction of body weight and improvements of glucose and lipid metabolism [2]. People suffering from the metabolic syndrome have higher baseline circulating FGF21 levels and exhibit a larger increase of plasma FGF21 concentrations following an oral fructose load. In contrast, the increase of FGF21 after ingestion of the same amount of glucose was delayed and much more modest. These results are paradoxical in that the metabolic effects of FGF-21 appear to be mainly beneficial while those of dietary fructose are generally deleterious [3]. The authors suggest the possibility that obese subjects with metabolic syndrome are resistant to the actions of FGF21 (akin to augmentation of circulating insulin and leptin concentrations and responses in insulin and leptin resistance) and that the exaggerated response to fructose ingestion may be a compensatory response [1]. The increases of FGF-21 in response to fructose ingestion across normal weight and overweight/obese subjects was significantly correlated with circulating insulin and glucose levels in response to oral glucose loads suggesting a relationship between FGF21 and insulin senstivity/glucose tolerance. Together, these novel results shed light on a potential mechanism related to the adverse metabolic effects of dietary fructose and raise new questions about the nutritional regulation of metabolic responses to dietary macronutrients, specifically sugars.Fructose is a major component of Western diets, and mounting evidence points to an obesogenic role for fructose via generation of substrates for de novo lipogenesis through rapid hepatic metabolism [3]. To understand how fructose may mediate its deleterious effects on various tissues, the authors proposed an intriguing novel hypothesis; fructose may acutely increase the production and secretion of FGF21 by potently activating the transcription factor carbohydrate response element-binding protein (ChREBP). In their study, Dushay et al. monitored circulating FGF21 levels after ingestion of a large (75 g) fructose bolus in 21 patients, half of them lean and healthy and half of them overweight to obese and insulin resistant [1]. Although FGF21 increased rapidly and sharply within 2 h and returned to baseline levels within 5 h in all patients, the response to fructose varied widely between the subjects. These findings point to individual differences in fructose absorption, metabolism and/or sensing. If that is the case, it would be important to understand whether an individual's susceptibility to develop diabetes may be predicted by a fructose tolerance test. If so, availability of such a test would help prevent onset of metabolic disease in subjects at risk by early personalized life style intervention and treatment.
