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      Is Open Access

      Testosterone treatment is associated with reduced adipose tissue dysfunction and nonalcoholic fatty liver disease in obese hypogonadal men

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          Abstract

          Purpose

          In both preclinical and clinical settings, testosterone treatment (TTh) of hypogonadism has shown beneficial effects on insulin sensitivity and visceral and liver fat accumulation. This prospective, observational study was aimed at assessing the change in markers of fat and liver functioning in obese men scheduled for bariatric surgery.

          Methods

          Hypogonadal patients with consistent symptoms ( n = 15) undergoing 27.63 ± 3.64 weeks of TTh were compared to untreated eugonadal ( n = 17) or asymptomatic hypogonadal ( n = 46) men. A cross-sectional analysis among the different groups was also performed, especially for data derived from liver and fat biopsies. Preadipocytes isolated from adipose tissue biopsies were used to evaluate insulin sensitivity, adipogenic potential and mitochondrial function. NAFLD was evaluated by triglyceride assay and by calculating NAFLD activity score in liver biopsies.

          Results

          In TTh-hypogonadal men, histopathological NAFLD activity and steatosis scores, as well as liver triglyceride content were lower than in untreated-hypogonadal men and comparable to eugonadal ones. TTh was also associated with a favorable hepatic expression of lipid handling-related genes. In visceral adipose tissue and preadipocytes, TTh was associated with an increased expression of lipid catabolism and mitochondrial bio-functionality markers. Preadipocytes from TTh men also exhibited a healthier morpho-functional phenotype of mitochondria and higher insulin-sensitivity compared to untreated-hypogonadal ones.

          Conclusions

          The present data suggest that TTh in severely obese, hypogonadal individuals induces metabolically healthier preadipocytes, improving insulin sensitivity, mitochondrial functioning and lipid handling. A potentially protective role for testosterone on the progression of NAFLD, improving hepatic steatosis and reducing intrahepatic triglyceride content, was also envisaged.

          Clinical Trial Registration

          ClinicalTrials.gov Identifier: NCT02248467, September 25th 2014

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          Most cited references106

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          Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method.

          Kenneth Livak, Thomas D. Schmittgen (2001)
          The two most commonly used methods to analyze data from real-time, quantitative PCR experiments are absolute quantification and relative quantification. Absolute quantification determines the input copy number, usually by relating the PCR signal to a standard curve. Relative quantification relates the PCR signal of the target transcript in a treatment group to that of another sample such as an untreated control. The 2(-Delta Delta C(T)) method is a convenient way to analyze the relative changes in gene expression from real-time quantitative PCR experiments. The purpose of this report is to present the derivation, assumptions, and applications of the 2(-Delta Delta C(T)) method. In addition, we present the derivation and applications of two variations of the 2(-Delta Delta C(T)) method that may be useful in the analysis of real-time, quantitative PCR data. Copyright 2001 Elsevier Science (USA).
          Article 0 comments Cited 23362 times – based on 0 reviews     Review now
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            Fiji: an open-source platform for biological-image analysis.

            Johannes Schindelin, Ignacio Arganda-Carreras, Erwin Frise … (2019)
            Fiji is a distribution of the popular open-source software ImageJ focused on biological-image analysis. Fiji uses modern software engineering practices to combine powerful software libraries with a broad range of scripting languages to enable rapid prototyping of image-processing algorithms. Fiji facilitates the transformation of new algorithms into ImageJ plugins that can be shared with end users through an integrated update system. We propose Fiji as a platform for productive collaboration between computer science and biology research communities.
            Article 0 comments Cited 13713 times – based on 0 reviews     Review now
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              Is Open Access

              NAFLD: a multisystem disease.

              Christopher Byrne, Giovanni Targher (2015)
              Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in Western countries that is predicted to become also the most frequent indication for liver transplantation by 2030. Over the last decade, it has been shown that the clinical burden of NAFLD is not only confined to liver-related morbidity and mortality, but there is now growing evidence that NAFLD is a multisystem disease, affecting extra-hepatic organs and regulatory pathways. For example, NAFLD increases risk of type 2 diabetes mellitus (T2DM), cardiovascular (CVD) and cardiac diseases, and chronic kidney disease (CKD). Although the primary liver pathology in NAFLD affects hepatic structure and function to cause morbidity and mortality from cirrhosis, liver failure and hepatocellular carcinoma, the majority of deaths among NAFLD patients are attributable to CVD. This narrative review focuses on the rapidly expanding body of clinical evidence that supports the concept of NAFLD as a multisystem disease. The review discusses the factors involved in the progression of liver disease in NAFLD and the factors linking NAFLD with other extra-hepatic chronic diseases, such as T2DM, CVD, cardiac diseases and CKD. The review will not discuss NAFLD treatments as these are discussed elsewhere in this issue of the Journal. For this review, PubMed was searched for articles using the keywords "non-alcoholic fatty liver disease" or "fatty liver" combined with "diabetes", "cardiovascular (or cardiac) disease", "cardiovascular mortality" or "chronic kidney disease" between 1990 and 2014. Articles published in languages other than English were excluded.
              Article 0 comments Cited 738 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                L. Vignozzi:
                ORCID: http://orcid.org/0000-0003-0907-0630
                linda.vignozzi@unifi.it
                Journal
                Journal ID (nlm-ta): J Endocrinol Invest
                Journal ID (iso-abbrev): J Endocrinol Invest
                Title: Journal of Endocrinological Investigation
                Publisher: Springer International Publishing (Cham )
                ISSN (Print): 0391-4097
                ISSN (Electronic): 1720-8386
                Publication date (Electronic): 8 August 2020
                Publication date PMC-release: 8 August 2020
                Publication date (Print): 2021
                Volume: 44
                Issue: 4
                Pages: 819-842
                Affiliations
                [1 ]GRID grid.8404.8, ISNI 0000 0004 1757 2304, Andrology, Women’s Endocrinology and Gender Incongruence Unit, Department of Experimental Clinical and Biomedical Sciences “Mario Serio”, , University of Florence, ; Viale Pieraccini 6, 50134 Florence, Italy
                [2 ]GRID grid.8404.8, ISNI 0000 0004 1757 2304, Interdepartmental Laboratory of Functional and Cellular Pharmacology of Reproduction, , University of Florence, ; Viale Pieraccini 6, 50134 Florence, Italy
                [3 ]GRID grid.8404.8, ISNI 0000 0004 1757 2304, Gastroenterology Unit, Department of Experimental Clinical and Biomedical Sciences “Mario Serio”, , University of Florence, ; Viale Pieraccini 6, 50134 Florence, Italy
                [4 ]GRID grid.8404.8, ISNI 0000 0004 1757 2304, Endocrinology Unit, Department of Experimental Clinical and Biomedical Sciences “Mario Serio”, , University of Florence, ; Viale Pieraccini 6, 50134 Florence, Italy
                [5 ]GRID grid.415219.a, General, Bariatric and Metabolic Surgery Unit, , Santa Maria Nuova Hospital, ; , Piazza Santa Maria Nuova, 1, 50122 Florence, Italy
                [6 ]Medical Affairs, Bayer AG, Kaiser-Wilhelm-Allee 1, 51373 Leverkusen, Germany
                [7 ]GRID grid.419691.2, ISNI 0000 0004 1758 3396, I.N.B.B. (Istituto Nazionale Biostrutture E Biosistemi), ; Viale delle Medaglie d’Oro 305, 00136 Rome, Italy
                Author information
                http://orcid.org/0000-0003-0907-0630
                Article
                Publisher ID: 1381
                DOI: 10.1007/s40618-020-01381-8
                PMC ID: 7946690
                PubMed ID: 32772323
                SO-VID: c0408b9c-fef3-4002-bf06-cc729fe6fe00
                Copyright © © The Author(s) 2020
                License:

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                Date received : 23 March 2020
                Date accepted : 31 July 2020
                Categories
                Subject: Original Article
                Custom metadata
                issue-copyright-statement © Italian Society of Endocrinology (SIE) 2021

                Keywords: testosterone,adipose tissue,liver,nafld,obesity,hypogonadism
                Data availability:
                Keywords: testosterone, adipose tissue, liver, nafld, obesity, hypogonadism

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