PMID- 36060961 OWN - NLM STAT- MEDLINE DCOM- 20220908 LR - 20220913 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 13 DP - 2022 TI - Distinct impacts of fat and fructose on the liver, muscle, and adipose tissue metabolome: An integrated view. PG - 898471 LID - 10.3389/fendo.2022.898471 [doi] LID - 898471 AB - OBJECTIVE: In 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. METHODS: We 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. RESULTS: HFat 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. CONCLUSIONS: Our data illustrate that HFat and HFruct have a negative but distinct impact on the metabolome of the liver, muscle, WAT, and BAT. CI - Copyright (c) 2022 Meneses, Sousa-Lima, Jarak, Raposo, Alves and Macedo. FAU - Meneses, Maria Joao AU - Meneses MJ AD - iNOVA4Health, NOVA Medical School/Faculdade de Ciencias Medicas (NMS/FCM), Universidade Nova de Lisboa, Lisbon, Portugal. AD - Portuguese Diabetes Association - Education and Research Center (APDP-ERC), Lisbon, Portugal. FAU - Sousa-Lima, Ines AU - Sousa-Lima I AD - iNOVA4Health, NOVA Medical School/Faculdade de Ciencias Medicas (NMS/FCM), Universidade Nova de Lisboa, Lisbon, Portugal. FAU - Jarak, Ivana AU - Jarak I AD - Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal. AD - Department of Anatomy and Unit for Multidisciplinary Research in Biomedicine (UMIB), Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal. FAU - Raposo, Joao F AU - Raposo JF AD - iNOVA4Health, NOVA Medical School/Faculdade de Ciencias Medicas (NMS/FCM), Universidade Nova de Lisboa, Lisbon, Portugal. AD - Portuguese Diabetes Association - Education and Research Center (APDP-ERC), Lisbon, Portugal. FAU - Alves, Marco G AU - Alves MG AD - Department of Anatomy and Unit for Multidisciplinary Research in Biomedicine (UMIB), Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal. FAU - Macedo, Maria Paula AU - Macedo MP AD - iNOVA4Health, NOVA Medical School/Faculdade de Ciencias Medicas (NMS/FCM), Universidade Nova de Lisboa, Lisbon, Portugal. AD - Portuguese Diabetes Association - Education and Research Center (APDP-ERC), Lisbon, Portugal. AD - Medical Sciences Department, University of Aveiro, Aveiro, Portugal. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220817 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 30237-26-4 (Fructose) RN - IY9XDZ35W2 (Glucose) SB - IM MH - Adipose Tissue, Brown/metabolism MH - Animals MH - *Diabetes Mellitus, Type 2/metabolism MH - *Fructose/adverse effects MH - Glucose/metabolism MH - Liver/metabolism MH - Male MH - Metabolome MH - Mice MH - Mice, Inbred C57BL MH - Muscles PMC - PMC9428722 OTO - NOTNLM OT - adipose tissue OT - diet OT - metabolomics OT - muscle OT - non-alcoholic fatty liver disease OT - prediabetes COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer RS declared a shared affiliation with the author MA to the handling editor at the time of review. EDAT- 2022/09/06 06:00 MHDA- 2022/09/09 06:00 PMCR- 2022/01/01 CRDT- 2022/09/05 04:01 PHST- 2022/03/17 00:00 [received] PHST- 2022/07/12 00:00 [accepted] PHST- 2022/09/05 04:01 [entrez] PHST- 2022/09/06 06:00 [pubmed] PHST- 2022/09/09 06:00 [medline] PHST- 2022/01/01 00:00 [pmc-release] AID - 10.3389/fendo.2022.898471 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2022 Aug 17;13:898471. doi: 10.3389/fendo.2022.898471. eCollection 2022.