دورية أكاديمية
A randomized 3-way crossover study indicates that high-protein feeding induces de novo lipogenesis in healthy humans.
| العنوان: | A randomized 3-way crossover study indicates that high-protein feeding induces de novo lipogenesis in healthy humans. |
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| المؤلفون: | Charidemou E; Department of Biochemistry and Cambridge Systems Biology Centre, University of Cambridge, Cambridge, United Kingdom., Ashmore T; Department of Biochemistry and Cambridge Systems Biology Centre, University of Cambridge, Cambridge, United Kingdom., Li X; Department of Biochemistry and Cambridge Systems Biology Centre, University of Cambridge, Cambridge, United Kingdom., McNally BD; Department of Biochemistry and Cambridge Systems Biology Centre, University of Cambridge, Cambridge, United Kingdom., West JA; Division of Gastroenterology and Hepatology, Department of Medicine, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom., Liggi S; Department of Biochemistry and Cambridge Systems Biology Centre, University of Cambridge, Cambridge, United Kingdom., Harvey M; Medical Research Council - Elsie Widdowson Laboratory, Cambridge, United Kingdom., Orford E; Medical Research Council - Elsie Widdowson Laboratory, Cambridge, United Kingdom., Griffin JL; Department of Biochemistry and Cambridge Systems Biology Centre, University of Cambridge, Cambridge, United Kingdom.; Computational and Systems Medicine, Surgery and Cancer, Imperial College London, London, United Kingdom. |
| المصدر: | JCI insight [JCI Insight] 2019 May 30; Vol. 4 (12). Date of Electronic Publication: 2019 May 30 (Print Publication: 2019). |
| نوع المنشور: | Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Society for Clinical Investigation Country of Publication: United States NLM ID: 101676073 Publication Model: eCollection Cited Medium: Internet ISSN: 2379-3708 (Electronic) Linking ISSN: 23793708 NLM ISO Abbreviation: JCI Insight Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Ann Arbor, Michigan : American Society for Clinical Investigation, [2016]- |
| مواضيع طبية MeSH: | Lipogenesis*, Diet, High-Protein/*adverse effects , Feeding Behavior/*physiology , Liver/*metabolism , Triglycerides/*biosynthesis, Administration, Oral ; Adult ; Amino Acids/administration & dosage ; Amino Acids/adverse effects ; Diabetes Mellitus, Type 2/metabolism ; Diabetes Mellitus, Type 2/prevention & control ; Dietary Proteins/administration & dosage ; Dietary Proteins/adverse effects ; Healthy Volunteers ; Hepatocytes/metabolism ; Humans ; Insulin/metabolism ; Insulin Resistance/physiology ; Liver/cytology ; Male ; Non-alcoholic Fatty Liver Disease/metabolism ; Non-alcoholic Fatty Liver Disease/prevention & control ; Obesity/etiology ; Obesity/metabolism ; Triglycerides/blood ; Young Adult |
| مستخلص: | BACKGROUNDDietary changes have led to the growing prevalence of type 2 diabetes and nonalcoholic fatty liver disease. A hallmark of both disorders is hepatic lipid accumulation, derived in part from increased de novo lipogenesis. Despite the popularity of high-protein diets for weight loss, the effect of dietary protein on de novo lipogenesis is poorly studied. We aimed to characterize the effect of dietary protein on de novo lipid synthesis.METHODSWe use a 3-way crossover interventional study in healthy males to determine the effect of high-protein feeding on de novo lipogenesis, combined with in vitro models to determine the lipogenic effects of specific amino acids. The primary outcome was a change in de novo lipogenesis-associated triglycerides in response to protein feeding.RESULTSWe demonstrate that high-protein feeding, rich in glutamate, increases de novo lipogenesis-associated triglycerides in plasma (1.5-fold compared with control; P < 0.0001) and liver-derived very low-density lipoprotein particles (1.8-fold; P < 0.0001) in samples from human subjects (n = 9 per group). In hepatocytes, we show that glutamate-derived carbon is incorporated into triglycerides via palmitate. In addition, supplementation with glutamate, glutamine, and leucine, but not lysine, increased triglyceride synthesis and decreased glucose uptake. Glutamate, glutamine, and leucine increased activation of protein kinase B, suggesting that induction of de novo lipogenesis occurs via the insulin signaling cascade.CONCLUSIONThese findings provide mechanistic insight into how select amino acids induce de novo lipogenesis and insulin resistance, suggesting that high-protein feeding to tackle diabetes and obesity requires greater consideration.FUNDINGThe research was supported by UK Medical Research Council grants MR/P011705/1, MC_UP_A090_1006 and MR/P01836X/1. JLG is supported by the Imperial Biomedical Research Centre, National Institute for Health Research (NIHR). |
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| معلومات مُعتمدة: | MC_UP_A090_1006 United Kingdom MRC_ Medical Research Council; MR/P011705/1 United Kingdom MRC_ Medical Research Council; MR/P01836X/1 United Kingdom MRC_ Medical Research Council; United Kingdom DH_ Department of Health |
| فهرسة مساهمة: | Keywords: Amino acid metabolism; Diabetes; Metabolism; Obesity |
| المشرفين على المادة: | 0 (Amino Acids) 0 (Dietary Proteins) 0 (Insulin) 0 (Triglycerides) |
| تواريخ الأحداث: | Date Created: 20190531 Date Completed: 20200817 Latest Revision: 20210109 |
| رمز التحديث: | 20221213 |
| مُعرف محوري في PubMed: | PMC6629161 |
| DOI: | 10.1172/jci.insight.124819 |
| PMID: | 31145699 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 2379-3708 |
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| DOI: | 10.1172/jci.insight.124819 |