Table_1_Distinct impacts of fat and fructose on the liver, muscle, and adipose tissue metabolome: An integrated view.docx

ObjectiveIn the last years, changes in dietary habits have contributed to the increasing prevalence of metabolic disorders, such as non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM). The differential burden of lipids and fructose on distinct organs needs to be unveiled. Herein, we hypothesized that high-fat and high-fructose diets differentially affect the metabolome of insulin-sensitive organs such as the liver, muscle, and different adipose tissue depots.MethodsWe have studied the impact of 12 weeks of a control (11.50% calories from fat, 26.93% from protein, and 61.57% from carbohydrates), high-fat/sucrose (HFat), or high-fructose (HFruct) feeding on C57Bl/6J male mice. Besides glucose homeostasis, we analyzed the hepatic levels of glucose and lipid-metabolism-related genes and the metabolome of the liver, the muscle, and white (WAT) and brown adipose tissue (BAT) depots.ResultsHFat diet led to a more profound impact on hepatic glucose and lipid metabolism than HFruct, with mice presenting glucose intolerance, increased saturated fatty acids, and no glycogen pool, yet both HFat and HFruct presented hepatic insulin resistance. HFat diet promoted a decrease in glucose and lactate pools in the muscle and an increase in glutamate levels. While HFat had alterations in BAT metabolites that indicate increased thermogenesis, HFruct led to an increase in betaine, a protective metabolite against fructose-induced inflammation.ConclusionsOur data illustrate that HFat and HFruct have a negative but distinct impact on the metabolome of the liver, muscle, WAT, and BAT.

目标近年来，饮食结构的变化已导致代谢性疾病如非酒精性脂肪性肝病（NAFLD）和2型糖尿病（T2DM）的发病率逐渐上升。有必要揭示脂质和果糖对不同器官的差异化负担。本研究假设高脂和高果糖饮食对不同胰岛素敏感器官，如肝脏、肌肉及不同脂肪组织库的代谢组具有差异化影响。方法我们研究了为期12周的控制饮食（脂肪供能11.50%，蛋白质供能26.93%，碳水化合物供能61.57%）、高脂/蔗糖（HFat）或高果糖（HFruct）喂养对C57Bl/6J雄性小鼠的影响。除了分析葡萄糖稳态外，我们还研究了肝脏中葡萄糖和脂质代谢相关基因的水平，以及肝脏、肌肉、白色脂肪组织（WAT）和棕色脂肪组织（BAT）的代谢组。结果HFat饮食相较于HFruct饮食对肝脏的葡萄糖和脂质代谢影响更为显著，表现为小鼠出现葡萄糖耐量降低、饱和脂肪酸水平增加、无糖原池，同时HFat和HFruct均导致肝脏胰岛素抵抗。HFat饮食促进肌肉中葡萄糖和乳酸池的减少，以及谷氨酸水平的升高。HFat饮食在BAT代谢物中的改变表明了热生成作用的增加，而HFruct饮食则导致胆碱水平升高，这是一种保护性代谢物，可抵抗果糖诱导的炎症。结论我们的数据显示，HFat和HFruct对肝脏、肌肉、WAT和BAT的代谢组均有负面影响，但作用机制存在差异。