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Roca-Rivada A, Do Cruzeiro M, Denis RG, Zhang Q, Rouault C, Rouillé Y, Launay JM, Cruciani-Guglielmacci C, Mattot V, Clément K, Jockers R, Dam J. Whole-body deletion of Endospanin 1 protects from obesity-associated deleterious metabolic alterations. JCI Insight 2024; 9:e168418. [PMID: 38716728 PMCID: PMC11141941 DOI: 10.1172/jci.insight.168418] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Accepted: 03/27/2024] [Indexed: 05/12/2024] Open
Abstract
The importance of the proper localization of most receptors at the cell surface is often underestimated, although this feature is essential for optimal receptor response. Endospanin 1 (Endo1) (also known as OBRGRP or LEPROT) is a protein generated from the same gene as the human leptin receptor and regulates the trafficking of proteins to the surface, including the leptin receptor. The systemic role of Endo1 on whole-body metabolism has not been studied so far. Here, we report that general Endo1-KO mice fed a high-fat diet develop metabolically healthy obesity with lipid repartitioning in organs and preferential accumulation of fat in adipose tissue, limited systematic inflammation, and better controlled glucose homeostasis. Mechanistically, Endo1 interacts with the lipid translocase CD36, thus regulating its surface abundance and lipid uptake in adipocytes. In humans, the level of Endo1 transcripts is increased in the adipose tissue of patients with obesity, but low levels rather correlate with a profile of metabolically healthy obesity. We suggest here that Endo1, most likely by controlling CD36 cell surface abundance and lipid uptake in adipocytes, dissociates obesity from diabetes and that its absence participates in metabolically healthy obesity.
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Affiliation(s)
- Arturo Roca-Rivada
- Institut Cochin, Inserm U1016, CNRS UMR 8104, Université Paris Cité, F-75014 Paris, France
| | - Marcio Do Cruzeiro
- Institut Cochin, Inserm U1016, CNRS UMR 8104, Université Paris Cité, F-75014 Paris, France
| | - Raphaël G.P. Denis
- Institut Cochin, Inserm U1016, CNRS UMR 8104, Université Paris Cité, F-75014 Paris, France
- Unité de Biologie Fonctionnelle et Adaptative, Université Paris Cité, CNRS, 75013 Paris, France
| | - Qiang Zhang
- Institut Cochin, Inserm U1016, CNRS UMR 8104, Université Paris Cité, F-75014 Paris, France
| | - Christine Rouault
- Sorbonne Université, Inserm, Nutrition and obesities: systemic approaches, Nutriomics, Department of Nutrition, Pitié-Salpêtrière Hospital, Assistance Publique Hopitaux de Paris, Paris, France
| | - Yves Rouillé
- Université de Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille, F-59000, Lille, France
| | | | | | - Virginie Mattot
- Université Paris Cité, Inserm, CHU Lille, Laboratory of Development and Plasticity of the Neuroendocrine Brain, Lille Neuroscience & Cognition, UMR-S1172, EGID, F-59000, Lille, France
| | - Karine Clément
- Sorbonne Université, Inserm, Nutrition and obesities: systemic approaches, Nutriomics, Department of Nutrition, Pitié-Salpêtrière Hospital, Assistance Publique Hopitaux de Paris, Paris, France
| | - Ralf Jockers
- Institut Cochin, Inserm U1016, CNRS UMR 8104, Université Paris Cité, F-75014 Paris, France
| | - Julie Dam
- Institut Cochin, Inserm U1016, CNRS UMR 8104, Université Paris Cité, F-75014 Paris, France
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Paczkowska-Abdulsalam M, Kretowski A. Obesity, metabolic health and omics: Current status and future directions. World J Diabetes 2021; 12:420-436. [PMID: 33889288 PMCID: PMC8040086 DOI: 10.4239/wjd.v12.i4.420] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2021] [Revised: 02/22/2021] [Accepted: 03/30/2021] [Indexed: 02/06/2023] Open
Abstract
The growing obesity epidemic is becoming a major public health concern, and the associated costs represent a considerable burden on societies. Among the most common complications of severe obesity are the development of hypertension, dyslipidemia, type 2 diabetes, cardiovascular disease, and various types of cancer. Interestingly, some obese individuals have a favorable metabolic profile and appear to be somehow protected from the detrimental effects of excessive adipose tissue accumulation. These individuals remain normoglycemic, insulin sensitive, and hypotensive with proper blood lipid levels, despite their high body mass index and/or waist circumference. Multiple independent observations have led to the concept of the metabolically healthy obese (MHO) phenotype, yet no consensus has been reached to date regarding a universal definition or the main mechanism behind this phenomenon. Recent technological advances and the use of high-throughput analysis techniques have revolutionized different areas of biomedical research. A multi-omics approach, which is used to investigate changes at different molecular levels in an organism or tissue, may provide valuable insights into the interplay between the molecules or pathways and the roles of different factors involved in the mechanisms underlying metabolic health deterioration. The aim of this review is to present the current status regarding the use of omics technologies to investigate the MHO phenotype, as well as the results of targeted analyses conducted in MHO individuals.
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Affiliation(s)
| | - Adam Kretowski
- Clinical Research Centre, Medical University of Bialystok, Bialystok 15-276, Poland
- Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Bialystok, Bialystok 15-276, Poland
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