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      The Expression of LEP, LEPR, IGF1 and IL10 in Obesity and the Relationship with microRNAs

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          Abstract

          Obesity is a multifactorial disease, with epigenetic alterations. Have been described modifications in the expression of some microRNAs, and some proteins related to obesity. The objective was to determine and correlate, in obese patients, the gene expression of LEP, LEPR, IGF1, IL10 and of miR-27a, miR-27b, miR-143 and miR-145. RNA was extracted from biopsies of subcutaneous fat, liver and visceral fat of 15 obese subjects submitted to bariatric surgery and of 15 non-obese subjects submitted to cholecystectomy for cDNA synthesis and for RT-PCR. The microRNAs were chosen using the TargetScan software. An increased expression of LEP and IGF1 was detected in the subcutaneous fat of the obese group compared to control, while the expression of IGF1 was higher in the control group than in the obese one. MiRNA-27a had a higher expression in the omentum of the obese patients and there was also a correlation in the expression of miRNA-145 and LEPR in the omentum of this group.

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          Obesity-induced overexpression of miRNA-143 inhibits insulin-stimulated AKT activation and impairs glucose metabolism.

          Sabine Jordan, Markus Krüger, Diana M Willmes … (2011)
          The contribution of altered post-transcriptional gene silencing to the development of insulin resistance and type 2 diabetes mellitus so far remains elusive. Here, we demonstrate that expression of microRNA (miR)-143 and 145 is upregulated in the liver of genetic and dietary mouse models of obesity. Induced transgenic overexpression of miR-143, but not miR-145, impairs insulin-stimulated AKT activation and glucose homeostasis. Conversely, mice deficient for the miR-143-145 cluster are protected from the development of obesity-associated insulin resistance. Quantitative-mass-spectrometry-based analysis of hepatic protein expression in miR-143-overexpressing mice revealed miR-143-dependent downregulation of oxysterol-binding-protein-related protein (ORP) 8. Reduced ORP8 expression in cultured liver cells impairs the ability of insulin to induce AKT activation, revealing an ORP8-dependent mechanism of AKT regulation. Our experiments provide direct evidence that dysregulated post-transcriptional gene silencing contributes to the development of obesity-induced insulin resistance, and characterize the miR-143-ORP8 pathway as a potential target for the treatment of obesity-associated diabetes. © 2011 Macmillan Publishers Limited. All rights reserved
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            miR-27a is a negative regulator of adipocyte differentiation via suppressing PPARgamma expression.

            Sang Yun Kim, A Kim, Hyun Lee … (2010)
            microRNAs (miRNAs) are non-coding small RNAs regulating gene expression, cell growth, and differentiation. Although several miRNAs have been implicated in cell growth and differentiation, it is barely understood their roles in adipocyte differentiation. In the present study, we reveal that miR-27a is involved in adipocyte differentiation by binding to the PPARgamma 3'-UTR whose sequence motifs are highly conserved in mammals. During adipogenesis, the expression level of miR-27a was inversely correlated with that of adipogenic marker genes such as PPARgamma and adiponectin. In white adipose tissue, miR-27a was more abundantly expressed in stromal vascular cell fraction than in mature adipocyte fraction. Ectopic expression of miR-27a in 3T3-L1 pre-adipocytes repressed adipocyte differentiation by reducing PPARgamma expression. Interestingly, the level of miR-27a in mature adipocyte fraction of obese mice was down-regulated than that of lean mice. Together, these results suggest that miR-27a would suppress adipocyte differentiation through targeting PPARgamma and thereby down-regulation of miR-27a might be associated with adipose tissue dysregulation in obesity.
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              Bariatric surgery worldwide 2003.

              J. Williams, Henry Buchwald (2004)
              There is a world epidemic of overweight, obesity, and morbid obesity, encompassing 1.7 billion people. Bariatric surgery today is the only effective therapy for morbid obesity. E-mail requests for information were sent to the presidents of the national societies of the 31 International Federation for the Surgery of Obesity (IFSO) nations, or national groupings, plus Sweden. Responses were tabulated; calculation of relative prevalence of specific procedures was done by weighted averages. Responders were 26 of 32 (81%) for the general questions and 24 of 32 (75%) for the question on specific operative percentages. In the year 2002-2003, 146,301 bariatric surgery operations were performed by 2,839 bariatric surgeons; 103,000 of these operations were performed in USA/Canada by 850 surgeons. The earliest start date for bariatric surgery was 1953 in the USA; IFSO was founded in 1995. In the year 2002-2003, 37.15% of operations were open; 62.85% laparoscopic. The 6 most popular procedures by weighted averages were: laparoscopic gastric bypass, 25.67%; laparoscopic adjustable gastric banding, 24.14%; open gastric bypass, 23.07%; laparoscopic long-limb gastric bypass, 8.9%; open long-limb gastric bypass, 7.45%; and open vertical banded gastroplasty, 4.25%. Pooling open and laparoscopic procedures, relative percentages were: gastric bypass, 65.11%; gastric banding, 24.41%; vertical banded gastroplasty, 5.43%; and biliopancreatic diversion/duodenal switch, 4.85%. Categorizing into restrictive/malabsorptive, purely restrictive, and primarily malabsorptive, the relative distribution of procedures was 65.11%, 29.84%, and 4.85%, respectively. The number of countries performing gastric banding was 23 (95%), gastric bypass 21 (88%), vertical banded gastroplasty 19 (79%), and biliopancreatic diversion/duodenal switch 16 (67%). Purely restrictive procedures were performed in 24 (100%) of the countries, restrictive/malabsorptive in 21 (88%), and primarily malabsorptive in 18 (75%). Bariatric surgery is expanding exponentially to meet the global epidemic of morbid obesity. Operative procedures in bariatric surgery are in flux and specific geographic trends and shifts are evident. Yet, of the patients qualifying for surgery, only about 1% are receiving this therapy--the only effective treatment currently available.
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                Author and article information

                Contributors
                Josep Bassaganya-Riera: Role: Editor
                Journal
                Journal ID (nlm-ta): PLoS One
                Journal ID (iso-abbrev): PLoS ONE
                Journal ID (publisher-id): plos
                Journal ID (pmc): plosone
                Title: PLoS ONE
                Publisher: Public Library of Science (San Francisco, USA )
                ISSN (Electronic): 1932-6203
                Publication date Collection: 2014
                Publication date (Electronic): 1 April 2014
                Volume: 9
                Issue: 4
                Electronic Location Identifier: e93512
                Affiliations
                [1 ]Department of Surgery and Anatomy of the Faculty of Medicine of Ribeirao Preto, University of São Paulo, Ribeirao Preto, SP, Brazil
                [2 ]Department of Surgery and Anatomy of the Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirao Preto, SP, Brazil
                [3 ]Department of Surgery and Anatomy of the Faculty of Medicine of Ribeirão Preto, University of São Paulo and Laboratory of Molecular Biology, Ribeirao Preto, SP, Brazil
                Virginia Tech, United States of America
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Performed the experiments: RVAC WSJ DPCT JSS. Analyzed the data: RVAC WSJ DPCT. Contributed reagents/materials/analysis tools: RVAC WSJ DPCT JSS. Wrote the paper: RVAC WSJ.

                Article
                Publisher ID: PONE-D-13-47494
                DOI: 10.1371/journal.pone.0093512
                PMC ID: 3972109
                PubMed ID: 24690978
                SO-VID: 023e0ec5-661a-4b1c-aa18-cfe750309661
                Copyright statement: Copyright @ 2014
                License:

                Collares et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                Date received : 12 November 2013
                Date accepted : 7 March 2014
                Page count
                Pages: 6
                Funding
                Research supported by Fundação Waldemar Barnsley Pessoa, Ribeirão Preto, SP, Brazil. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Subject: Research Article
                Subject: Biology and life sciences
                Subject: Biochemistry
                Subject: Hormones
                Subject: Cell Biology
                Subject: Molecular Cell Biology
                Subject: Developmental Biology
                Subject: Molecular Development
                Subject: Cytokines
                Subject: Genetics
                Subject: Epigenetics
                Subject: RNA interference
                Subject: Gene Expression
                Subject: Physiology
                Subject: Endocrine Physiology
                Subject: Growth Factors
                Subject: Physiological Parameters
                Subject: Body Weight
                Subject: Obesity
                Subject: Immunology
                Subject: Immune System
                Subject: Nutrition
                Subject: Medicine and Health Sciences
                Subject: Endocrinology

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                ScienceOpen disciplines: Uncategorized

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