Browse

You are looking at 1 - 10 of 14,349 items for

  • Refine by access: All content x
Clear All
Irena Audzeyenka Laboratory of Molecular and Cellular Nephrology, Mossakowski Medical Research Institute, Polish Academy of Sciences, Gdansk, Poland
Department of Molecular Biotechnology, Faculty of Chemistry, University of Gdansk, Gdansk, Poland

Search for other papers by Irena Audzeyenka in
Google Scholar
PubMed
Close
,
Patrycja Rachubik Laboratory of Molecular and Cellular Nephrology, Mossakowski Medical Research Institute, Polish Academy of Sciences, Gdansk, Poland

Search for other papers by Patrycja Rachubik in
Google Scholar
PubMed
Close
,
Dorota Rogacka Laboratory of Molecular and Cellular Nephrology, Mossakowski Medical Research Institute, Polish Academy of Sciences, Gdansk, Poland
Department of Molecular Biotechnology, Faculty of Chemistry, University of Gdansk, Gdansk, Poland

Search for other papers by Dorota Rogacka in
Google Scholar
PubMed
Close
,
Moin A Saleem Bristol Renal, University of Bristol, Dorothy Hodgkin Building, Bristol, United Kingdom

Search for other papers by Moin A Saleem in
Google Scholar
PubMed
Close
, and
Agnieszka Piwkowska Laboratory of Molecular and Cellular Nephrology, Mossakowski Medical Research Institute, Polish Academy of Sciences, Gdansk, Poland
Department of Molecular Biotechnology, Faculty of Chemistry, University of Gdansk, Gdansk, Poland

Search for other papers by Agnieszka Piwkowska in
Google Scholar
PubMed
Close

Diabetic nephropathy (DN) is one of the most frequent complications of diabetes. Early stages of DN are associated with hyperinsulinemia and progressive insulin resistance in insulin-sensitive cells, including podocytes. The diabetic environment induces pathological changes, especially in podocyte bioenergetics, which is tightly linked with mitochondrial dynamics. The regulatory role of insulin in mitochondrial morphology in podocytes has not been fully elucidated. Therefore, the main goal of the present study was to investigate effects of insulin on the regulation of mitochondrial dynamics and bioenergetics in human podocytes. Biochemical analyses were performed to assess oxidative phosphorylation efficiency by measuring the oxygen consumption rate (OCR) and glycolysis by measuring the extracellular acidification rate (ECAR). mRNA and protein expression were determined by real-time polymerase chain reaction and Western blot. The intracellular mitochondrial network was visualized by MitoTracker staining. All calculations were conducted using CellProfiler software. Short-term insulin exposure exerted inhibitory effects on various parameters of oxidative respiration and adenosine triphosphate production, and glycolysis flux was elevated. After a longer time of treating cells with insulin, an increase in mitochondrial size was observed, accompanied by a reduction of expression of the mitochondrial fission markers DRP1 and FIS1 and an increase in mitophagy. Overall, we identified a previously unknown role for insulin in the regulation of oxidative respiration and glycolysis and elucidated mitochondrial dynamics in human podocytes. The present results emphasize the importance of the duration of insulin stimulation for its metabolic and molecular effects, which should be considered in clinical and experimental studies of DN.

Restricted access
Caroline C Faria Instituto de Biofísica Carlos Chagas Filho, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

Search for other papers by Caroline C Faria in
Google Scholar
PubMed
Close
,
Leonardo Matta Pereira Instituto de Biofísica Carlos Chagas Filho, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

Search for other papers by Leonardo Matta Pereira in
Google Scholar
PubMed
Close
,
Luiz Gabriel Portilho Moreira Instituto de Biofísica Carlos Chagas Filho, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

Search for other papers by Luiz Gabriel Portilho Moreira in
Google Scholar
PubMed
Close
,
Kathelinie Celestino Faustino Instituto de Biofísica Carlos Chagas Filho, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

Search for other papers by Kathelinie Celestino Faustino in
Google Scholar
PubMed
Close
,
Milena Simões Peixoto Instituto de Biofísica Carlos Chagas Filho, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

Search for other papers by Milena Simões Peixoto in
Google Scholar
PubMed
Close
,
Ariclécio Cunha de Oliveira Instituto Superior de Ciências Biomédicas, Universidade Estadual do Ceará, Ceará, Brazil

Search for other papers by Ariclécio Cunha de Oliveira in
Google Scholar
PubMed
Close
,
Andrea Claudia Freitas Ferreira Instituto de Biofísica Carlos Chagas Filho, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
NUMPEX, Campus Duque de Caxias, UFRJ, Rio de Janeiro, Brazil

Search for other papers by Andrea Claudia Freitas Ferreira in
Google Scholar
PubMed
Close
,
Denise Pires Carvalho Instituto de Biofísica Carlos Chagas Filho, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

Search for other papers by Denise Pires Carvalho in
Google Scholar
PubMed
Close
, and
Rodrigo Soares Fortunato Instituto de Biofísica Carlos Chagas Filho, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

Search for other papers by Rodrigo Soares Fortunato in
Google Scholar
PubMed
Close

Thyroid disorders affect more women than men, but the underlying mechanisms contributing to this disparity remain incompletely understood. Thyrotropin (TSH), the primary regulator of thyroid oxidative hormonogenesis, has been implicated as a risk factor for proliferative thyroid diseases and a predictor of malignancy. In this study, we aimed to evaluate the impact of sustained elevated TSH levels on thyroid redox homeostasis, inflammatory markers, and DNA damage response in both male and female rats. Rats were treated with methimazole for 7 or 21 days, and hormonal measurements were conducted. H2O2 levels were evaluated in thyroid membrane fractions, while enzymatic activities were assessed in total thyroid homogenates. Sex-specific differences emerged, with females displaying higher reactive oxygen species levels – increased transiently NOX and sustained DUOX activities. Lipid peroxidation marker 4-hydroxynonenal (4-HNE) was elevated in females at both time points, contrasting with males just at 21 days. Sexual dimorphism was observed in DNA damage response, with females showing higher γH2AX levels at 21 days. Elevated IL-1β, TNF-α, CD11b mRNA, and phospho-NF-κB levels at 7 days indicated a distinct inflammatory profile in females. Notably, both sexes exhibited upregulated antioxidant enzymes. Our data suggest that females are more susceptible to oxidative damage and inflammation in our goiter model, which may be associated with higher ROS production and a less-efficient antioxidant defense system. These findings provide insights into the sex-specific mechanisms underlying thyroid dysfunction and highlight the importance of considering sex disparities in thyroid disorder research.

Restricted access
Jonathan D Douros Novo Nordisk Research Center Indianapolis, Indianapolis, Indiana, USA

Search for other papers by Jonathan D Douros in
Google Scholar
PubMed
Close
,
Jacek Mokrosinski Novo Nordisk Research Center Indianapolis, Indianapolis, Indiana, USA

Search for other papers by Jacek Mokrosinski in
Google Scholar
PubMed
Close
, and
Brian Finan Novo Nordisk Research Center Indianapolis, Indianapolis, Indiana, USA

Search for other papers by Brian Finan in
Google Scholar
PubMed
Close

The glucagon-like peptide 1 receptor (GLP-1R) is a class B G protein-coupled receptor (GPCR) that emerged as a pharmacologic target in cardiometabolic disease, including diabetes and obesity, over 30 years ago. The subsequent widespread clinical use of GLP-1R agonists, including exenatide, liraglutide, and semaglutide, has made the GLP-1R a preeminent model for understanding basic GPCR biology, including the emergent field of biased agonism. Recent data demonstrate that the dual GLP-1R/glucose dependent insulinotropic polypeptide receptor (GIPR) agonist tirzepatide exhibits a biased signaling profile characterized by preferential Gαs activation over β-arrestin recruitment, which appears to contribute to its insulinotropic and body-weight reducing effects in preclinical models. This constitutes a major finding in which nuanced, mechanistic receptor signaling dynamics in vitro mediate real-world clinical differentiation within a drug class. Because of the striking bench-top-to-bed side relevance of this biased signaling phenomenon, we have undertaken a review of the emerging data detailing biased agonism at the GLP-1R. In this review, we introduce the core concept of biased agonism followed by a detailed consideration of the key mechanisms, including ligand-mediated bias, receptor-mediated bias, and systems/cell-type bias. Current industry programs are largely, if not entirely, focused on developing biased ligands, and so we have dedicated a section of the review to a brief meta-analysis of compounds reported to drive biased signaling, with a consideration of the structural determinants of receptor–ligand interactions. In this work, we aim to assess the current knowledge regarding signaling bias at the GLP-1R and how these ideas might be leveraged in future optimization.

Restricted access
Eugenie Macfarlane Bone Research Program, ANZAC Research Institute, The University of Sydney, Australia

Search for other papers by Eugenie Macfarlane in
Google Scholar
PubMed
Close
,
Hong Zhou Bone Research Program, ANZAC Research Institute, The University of Sydney, Australia

Search for other papers by Hong Zhou in
Google Scholar
PubMed
Close
, and
Markus J Seibel Bone Research Program, ANZAC Research Institute, The University of Sydney, Australia
Department of Endocrinology and Metabolism, Concord Repatriation General Hospital, Sydney, Australia

Search for other papers by Markus J Seibel in
Google Scholar
PubMed
Close

Glucocorticoids are steroid hormones, secreted by the adrenals to regulate a range of metabolic, immunologic, and homeostatic functions. Due to their potent anti-inflammatory effects, synthetic glucocorticoids are widely used to treat inflammatory disorders. However, their use especially at high doses and over the long-term is associated with several unwanted side effects that compromises their intended use (e.g. glucocorticoid-induced osteoporosis and/or diabetes, myopathy, and skin atrophy). Both endogenous and synthetic glucocorticoids exert their effects through the glucocorticoid receptor, a transcription factor present in nearly all nucleated cells. Glucocorticoid receptor knockout mouse models have proved to be valuable tools in understanding how glucocorticoids contribute to skeletal health and disease. These models, described in this review, have helped to establish that the effects of glucocorticoids on the skeleton are multifaceted, cell specific and concentration dependent. Intriguingly, while endogenous glucocorticoids are essential for bone formation, high-dose exogenous glucocorticoids may induce bone loss. Additionally, the actions of endogenous glucocorticoids vary greatly depending on the disease microenvironment. For example, endogenous glucocorticoids have predominately beneficial anti-inflammatory effects in rheumatoid arthritis, but detrimental actions in osteoarthritis by driving cartilage loss and abnormal bone formation. Studies in tissue-specific knockout models provide important insights that will aid the development of new glucocorticoid therapeutics that can specifically target certain cell types to minimise unwanted effects from current glucocorticoid therapy.

Restricted access
Sonu Khanka Division of Endocrinology, CSIR-Central Drug Research Institute, Lucknow, India
Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, India

Search for other papers by Sonu Khanka in
Google Scholar
PubMed
Close
,
Charul Somani Department of Chemistry, Mohanlal Sukhadia University, Udaipur-Rajasthan, India

Search for other papers by Charul Somani in
Google Scholar
PubMed
Close
,
Kriti Sharma Division of Endocrinology, CSIR-Central Drug Research Institute, Lucknow, India
Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, India

Search for other papers by Kriti Sharma in
Google Scholar
PubMed
Close
,
Shivani Sharma Division of Endocrinology, CSIR-Central Drug Research Institute, Lucknow, India
Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, India

Search for other papers by Shivani Sharma in
Google Scholar
PubMed
Close
,
Akhilesh Kumar Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, India
Sophisticated Analytical Instrument Facility & Research, Division, CSIR-Central Drug Research Institute, Lucknow, India

Search for other papers by Akhilesh Kumar in
Google Scholar
PubMed
Close
,
Naibedya Chattopadhyay Division of Endocrinology, CSIR-Central Drug Research Institute, Lucknow, India
Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, India

Search for other papers by Naibedya Chattopadhyay in
Google Scholar
PubMed
Close
,
Sanjeev K Kanojiya Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, India
Sophisticated Analytical Instrument Facility & Research, Division, CSIR-Central Drug Research Institute, Lucknow, India

Search for other papers by Sanjeev K Kanojiya in
Google Scholar
PubMed
Close
,
Dinesh Kumar Yadav Department of Chemistry, Mohanlal Sukhadia University, Udaipur-Rajasthan, India

Search for other papers by Dinesh Kumar Yadav in
Google Scholar
PubMed
Close
, and
Divya Singh Division of Endocrinology, CSIR-Central Drug Research Institute, Lucknow, India
Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, India

Search for other papers by Divya Singh in
Google Scholar
PubMed
Close

Estrogen deficiency is one of the main causes for postmenopausal osteoporosis. Current osteoporotic therapies are of high cost and associated with serious side effects. So there is an urgent need for cost-effective anti-osteoporotic agents. Anti-osteoporotic activity of Litsea glutinosa extract (LGE) is less explored. Moreover, its role in fracture healing and mechanism of action is still unknown. In the present study we explore the osteoprotective potential of LGE in osteoblast cells and fractured and ovariectomized (Ovx) mice models. Alkaline phosphatase (ALP), MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and mineralization assays revealed that LGE treatment increased osteoblast cell differentiation, viability and mineralization. LGE treatment at 0.01 μg increased the expression of BMP2, PSMAD, RUNX2 and type 1 col. LGE also mitigated RANKL-induced osteoclastogenesis. Next, drill hole injury Balb/C mice model was treated with LGE for 12 days. Micro-CT analysis and Calcein labeling at the fracture site showed that LGE (20 mg/kg) enhanced new bone formation and bone regeneration, also increased expression of BMP2/SMAD1 signaling genes at fracture site. Ovx mice were treated with LGE for 1 month. μCT analysis indicated that the treatment of LGE at 20 mg/kg dose prevented the alteration in bone microarchitecture and maintained bone mineral density and bone mineral content. Treatment also increased bone strength and restored the bone turnover markers. Furthermore, in bone samples, LGE increased osteogenesis by enhancing the expression of BMP2/SMAD1 signaling components and decreased osteoclast number and surface. We conclude that LGE promotes osteogenesis via modulating the BMP2/SMAD1 signaling pathway. The study advocates the therapeutic potential of LGE in osteoporosis treatment.

Restricted access
Yaxiong Huang Department of Reproductive Medicine center, Zhongnan Hospital of Wuhan University, Wuhan, Hubei Province, PR China
Hubei Clinical Research Center for Prenatal Diagnosis and Birth Health, Wuhan Hubei Province, PR China
Wuhan Clinical Research Center for Reproductive Science and Birth Health, Wuhan Hubei Province, PR China
Department of Gynaecology and Obstetrics, Sinopharm Dongfeng Hospital, Hubei University of Medicine, Shiyan, Hubei Province, PR China

Search for other papers by Yaxiong Huang in
Google Scholar
PubMed
Close
,
Zihan Wang Department of Reproductive Medicine center, Zhongnan Hospital of Wuhan University, Wuhan, Hubei Province, PR China
Hubei Clinical Research Center for Prenatal Diagnosis and Birth Health, Wuhan Hubei Province, PR China
Wuhan Clinical Research Center for Reproductive Science and Birth Health, Wuhan Hubei Province, PR China

Search for other papers by Zihan Wang in
Google Scholar
PubMed
Close
,
Bin Li Department of Gynaecology and Obstetrics, Sinopharm Dongfeng Hospital, Hubei University of Medicine, Shiyan, Hubei Province, PR China

Search for other papers by Bin Li in
Google Scholar
PubMed
Close
,
Lina Ke Department of Gynaecology and Obstetrics, Sinopharm Dongfeng Hospital, Hubei University of Medicine, Shiyan, Hubei Province, PR China

Search for other papers by Lina Ke in
Google Scholar
PubMed
Close
,
Yao Xiong Department of Reproductive Medicine center, Zhongnan Hospital of Wuhan University, Wuhan, Hubei Province, PR China
Hubei Clinical Research Center for Prenatal Diagnosis and Birth Health, Wuhan Hubei Province, PR China
Wuhan Clinical Research Center for Reproductive Science and Birth Health, Wuhan Hubei Province, PR China

Search for other papers by Yao Xiong in
Google Scholar
PubMed
Close
, and
Yuanzhen Zhang Department of Reproductive Medicine center, Zhongnan Hospital of Wuhan University, Wuhan, Hubei Province, PR China
Hubei Clinical Research Center for Prenatal Diagnosis and Birth Health, Wuhan Hubei Province, PR China
Wuhan Clinical Research Center for Reproductive Science and Birth Health, Wuhan Hubei Province, PR China

Search for other papers by Yuanzhen Zhang in
Google Scholar
PubMed
Close

The impaired endometrial receptivity is a major factor contributing to infertility in patients with endometriosis (EM), but the underlying mechanism remains unclear. Our study aimed to investigate the role of Kruppel-like factor 15 (KLF15) in endometrial receptivity and its regulation in EM. We observed a significant decrease in KLF15 expression in the mid-secretory epithelial endometrial cells of EM patients compared to normal females without EM. To confirm the role of KLF15 in endometrial receptivity, we found a significantly reduced KLF15 expression and a significant decrease in embryo implantation number in the rat model via uterine horn infection with siRNA. This highlights the importance of KLF15 as a regulator receptivity. Furthermore, through ChIP-qPCR, we discovered that the progesterone receptor (PR) directly binds to KLF15 promoter regions, indicating that progesterone resistance may mediate the decrease in KLF15 expression in EM patients. Additionally, we found that the mid-secretory endometrium of EM patients exhibited impaired epithelial–mesenchymal transition (EMT). Knockdown of KLF15 upregulated E-cadherin and downregulated vimentin expression, leading to inhibited invasiveness and migration of Ishikawa cells. Overexpression KLF15 promotes EMT, invasiveness, and migration ability, and increases the attachment rate of JAR cells to Ishikawa cells. Through RNA-seq analysis, we identified TWIST2 as a downstream gene of KLF15. We confirmed that KLF15 directly binds to the promoter region of TWIST2 via ChIP-qPCR, promoting epithelial cell EMT during the establishment of endometrial receptivity. Our study reveals the involvement of KLF15 in the regulation of endometrial receptivity and its downstream effects on EMT. These findings provide valuable insights into potential therapeutic approaches for treating non-receptive endometrium in patients with EM.

Open access
Qin Yin Department of Orthopedics, Wuxi Ninth People’s Hospital Affiliated to Soochow University, Wuxi, Jiangsu, China

Search for other papers by Qin Yin in
Google Scholar
PubMed
Close
,
Jun Gu Department of Orthopedics, Wuxi Ninth People’s Hospital Affiliated to Soochow University, Wuxi, Jiangsu, China

Search for other papers by Jun Gu in
Google Scholar
PubMed
Close
,
Pengju Ren Department of Orthopedics, The Shanghai Tenth People’s Hospital of Tongji University, Shanghai, China

Search for other papers by Pengju Ren in
Google Scholar
PubMed
Close
,
Zhiqiang Guan Department of Dermatology, Xuzhou Municipal Hospital Affiliated to Xuzhou Medical University, Xuzhou, Jiangsu, China

Search for other papers by Zhiqiang Guan in
Google Scholar
PubMed
Close
,
Yongxiang Wang Department of Orthopedics, Clinical Medical College, Yangzhou University, Yangzhou, China
Department of Orthopedics, Northern Jiangsu People’s Hospital, Yangzhou, China

Search for other papers by Yongxiang Wang in
Google Scholar
PubMed
Close
,
Ruijun Bai Department of Orthopedics, Wuxi Ninth People’s Hospital Affiliated to Soochow University, Wuxi, Jiangsu, China

Search for other papers by Ruijun Bai in
Google Scholar
PubMed
Close
, and
Yu Liu Department of Orthopedics, Wuxi Ninth People’s Hospital Affiliated to Soochow University, Wuxi, Jiangsu, China

Search for other papers by Yu Liu in
Google Scholar
PubMed
Close

The role of this study was to evaluate the impact of gut microbiota depletion on the progression of osteoarthritis (OA) and osteoporosis (OP). We conducted an experimental mouse model of OA and OP over an 8-week period. The model involved destabilization of the medial meniscus and bilateral ovariectomy (OVX). To deplete the gut microbiota, we administered a course of antibiotics for 8 weeks. The severity of OA was assessed through micro-CT scanning, X-rays, and immunohistochemical staining. Microbiome analysis was performed using PCR of 16S DNA on fecal samples, and the levels of serum lipopolysaccharide, interleukin 6, tumor necrosis factor-α (TNF-α), osteocalcin, and estrogen were measured using enzyme-linked immunosorbent assay. We found that in comparison to the OVX+OA group, the OVX+OA+ABT group exhibited increased bone mineral density (P < 0.0001), bone volume fraction (P = 0.0051), and trabecular number (P = 0.0023) in the metaphyseal bone. Additionally, cartilage injury and levels of matrix metalloproteinase 13 were reduced in the OVX+OA+ABT group compared to the OVX+OA group. Moreover, the OVX+OA+ABT group demonstrated decreased relative abundance of Bacteroidetes, serum lipopolysaccharide (P = 0.0005), TNF-α (P < 0.0001), CTX-1 (P = 0.0002), and increased expression of bone formation markers. These findings were further supported by correlation network analyses. Depletion of gut microbiota was shown to protect against bone loss and cartilage degradation by modulating the composition of the gut microbiota in osteoporosis and osteoarthritis.

Restricted access
Thomas Willmott Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom

Search for other papers by Thomas Willmott in
Google Scholar
PubMed
Close
and
Elizabeth C Cottrell Maternal and Fetal Health Research Centre, Division of Developmental Biology & Medicine, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom

Search for other papers by Elizabeth C Cottrell in
Google Scholar
PubMed
Close

During pregnancy, all major physiological systems undergo remarkable changes, driven largely by alterations in the maternal hormonal milieu. In healthy pregnancies, maternal cardiovascular and metabolic adaptation to pregnancy occurs to support fetal growth and maternal well-being. Impaired maternal adaptation to pregnancy is associated with a range of pregnancy complications, including gestational diabetes and preeclampsia. There is growing recognition of the importance of different maternal microbiota, including in the gut, vagina and oral cavity, in supporting normal maternal adaptations to pregnancy as well as evidence for microbial disturbances associating with pregnancy pathologies. Here, we aim to summarise emerging evidence demonstrating that differences in maternal microbiota associate with pregnancy outcomes and discuss potential therapeutic approaches under development that might restore an ‘optimal’ microbiome. In particular, we highlight recent work by ourselves and others exploring the role of the oral microbiome in pregnancy, given established links between poor oral health (e.g. periodontitis) and adverse pregnancy outcomes. Our research has focussed on specific nitrate-reducing oral bacteria which play a role in the generation of nitric oxide (NO) and other bioactive nitrogen oxides associated with cardiovascular health and maternal cardiovascular adaption to pregnancy. Ongoing research aims to define whether altered microbial profiles have clinical utility in the prediction of pregnancy pathologies, and whether interventions designed to optimise specific maternal microbiota could help prevent future complications.

Restricted access
Ana Fernanda Castillo Departamento de Bioquímica Humana, Universidad de Buenos Aires, Facultad de Medicina, Buenos Aires, Argentina
CONICET – Universidad de Buenos Aires, Instituto de Investigaciones Biomédicas (INBIOMED), Buenos Aires, Argentina

Search for other papers by Ana Fernanda Castillo in
Google Scholar
PubMed
Close
,
Cecilia Poderoso Departamento de Bioquímica Humana, Universidad de Buenos Aires, Facultad de Medicina, Buenos Aires, Argentina
CONICET – Universidad de Buenos Aires, Instituto de Investigaciones Biomédicas (INBIOMED), Buenos Aires, Argentina
CONICET – Universidad de Buenos Aires, Instituto de Investigaciones Biomédicas (INBIOMED), Buenos Aires, Argentina

Search for other papers by Cecilia Poderoso in
Google Scholar
PubMed
Close
,
Paula Mariana Maloberti Departamento de Bioquímica Humana, Universidad de Buenos Aires, Facultad de Medicina, Buenos Aires, Argentina
CONICET – Universidad de Buenos Aires, Instituto de Investigaciones Biomédicas (INBIOMED), Buenos Aires, Argentina
CONICET – Universidad de Buenos Aires, Instituto de Investigaciones Biomédicas (INBIOMED), Buenos Aires, Argentina

Search for other papers by Paula Mariana Maloberti in
Google Scholar
PubMed
Close
,
Fabiana Cornejo Maciel Departamento de Bioquímica Humana, Universidad de Buenos Aires, Facultad de Medicina, Buenos Aires, Argentina
CONICET – Universidad de Buenos Aires, Instituto de Investigaciones Biomédicas (INBIOMED), Buenos Aires, Argentina

Search for other papers by Fabiana Cornejo Maciel in
Google Scholar
PubMed
Close
,
María Mercedes Mori Sequeiros Garcia Departamento de Bioquímica Humana, Universidad de Buenos Aires, Facultad de Medicina, Buenos Aires, Argentina
CONICET – Universidad de Buenos Aires, Instituto de Investigaciones Biomédicas (INBIOMED), Buenos Aires, Argentina

Search for other papers by María Mercedes Mori Sequeiros Garcia in
Google Scholar
PubMed
Close
,
Ulises Daniel Orlando CONICET – Universidad de Buenos Aires, Instituto de Investigaciones Biomédicas (INBIOMED), Buenos Aires, Argentina

Search for other papers by Ulises Daniel Orlando in
Google Scholar
PubMed
Close
,
Pablo Mele Departamento de Bioquímica Humana, Universidad de Buenos Aires, Facultad de Medicina, Buenos Aires, Argentina
CONICET – Universidad de Buenos Aires, Instituto de Investigaciones Biomédicas (INBIOMED), Buenos Aires, Argentina

Search for other papers by Pablo Mele in
Google Scholar
PubMed
Close
,
Yanina Benzo Departamento de Bioquímica Humana, Universidad de Buenos Aires, Facultad de Medicina, Buenos Aires, Argentina
CONICET – Universidad de Buenos Aires, Instituto de Investigaciones Biomédicas (INBIOMED), Buenos Aires, Argentina

Search for other papers by Yanina Benzo in
Google Scholar
PubMed
Close
,
Melina Andrea Dattilo Departamento de Bioquímica Humana, Universidad de Buenos Aires, Facultad de Medicina, Buenos Aires, Argentina
CONICET – Universidad de Buenos Aires, Instituto de Investigaciones Biomédicas (INBIOMED), Buenos Aires, Argentina

Search for other papers by Melina Andrea Dattilo in
Google Scholar
PubMed
Close
,
Jesica Prada CONICET – Universidad de Buenos Aires, Instituto de Investigaciones Biomédicas (INBIOMED), Buenos Aires, Argentina

Search for other papers by Jesica Prada in
Google Scholar
PubMed
Close
,
Luciano Quevedo CONICET – Universidad de Buenos Aires, Instituto de Investigaciones Biomédicas (INBIOMED), Buenos Aires, Argentina

Search for other papers by Luciano Quevedo in
Google Scholar
PubMed
Close
,
Matías Belluno CONICET – Universidad de Buenos Aires, Instituto de Investigaciones Biomédicas (INBIOMED), Buenos Aires, Argentina

Search for other papers by Matías Belluno in
Google Scholar
PubMed
Close
,
Cristina Paz Departamento de Bioquímica Humana, Universidad de Buenos Aires, Facultad de Medicina, Buenos Aires, Argentina
CONICET – Universidad de Buenos Aires, Instituto de Investigaciones Biomédicas (INBIOMED), Buenos Aires, Argentina

Search for other papers by Cristina Paz in
Google Scholar
PubMed
Close
, and
Ernesto Jorge Podesta Departamento de Bioquímica Humana, Universidad de Buenos Aires, Facultad de Medicina, Buenos Aires, Argentina
CONICET – Universidad de Buenos Aires, Instituto de Investigaciones Biomédicas (INBIOMED), Buenos Aires, Argentina

Search for other papers by Ernesto Jorge Podesta in
Google Scholar
PubMed
Close

For many years, research in the field of steroid synthesis has aimed to understand the regulation of the rate-limiting step of steroid synthesis, i.e. the transport of cholesterol from the outer to the inner mitochondrial membrane, and identify the protein involved in the conversion of cholesterol into pregnenolone. The extraordinary work by B Clark, J Wells, S R King, and D M Stocco eventually identified this protein and named it steroidogenic acute regulatory protein (StAR). The group’s finding was also one of the milestones in understanding the mechanism of nonvesicular lipid transport between organelles. A notable feature of StAR is its high degree of phosphorylation. In fact, StAR phosphorylation in the acute phase is required for full steroid biosynthesis. As a contribution to this subject, our work has led to the characterization of StAR as a substrate of kinases and phosphatases and as an integral part of a mitochondrion-associated multiprotein complex, essential for StAR function and cholesterol binding and mitochondrial transport to yield maximum steroid production. Results allow us to postulate the existence of a specific cellular microenvironment where StAR protein synthesis and activation, along with steroid synthesis and secretion, are performed in a compartmentalized manner, at the site of hormone receptor stimulation, and involving the compartmentalized formation of the steroid molecule-synthesizing complex.

Restricted access
Renata Risi R Risi, Experimental Medicine, University of Rome La Sapienza, Rome, Italy

Search for other papers by Renata Risi in
Google Scholar
PubMed
Close
,
Antonio J Vidal-Puig A Vidal-Puig, Metabolic Research Laboratories, Cambridge University, Cambridge, United Kingdom of Great Britain and Northern Ireland

Search for other papers by Antonio J Vidal-Puig in
Google Scholar
PubMed
Close
, and
Guillaume Bidault G Bidault, Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Cambridge University, Cambridge, United Kingdom of Great Britain and Northern Ireland

Search for other papers by Guillaume Bidault in
Google Scholar
PubMed
Close

Obesity and diabetes represent two increasing and invalidating public health issues that often coexist. It is acknowledged that fat mass excess predisposes to insulin resistance and type 2 diabetes mellitus (T2D), with the increasing incidence of the two diseases significantly associated. Moreover, emerging evidence suggests that obesity might also accelerate the appearance of type 1 diabetes (T1D), which is now a relatively frequent comorbidity in patients with obesity. It is a common clinical finding that not all patients with obesity will develop diabetes at the same level of adiposity, with gender, genetic, and ethnic factors playing an important role in defining the timing of diabetes appearance. The adipose tissue (AT) expandability hypothesis explains this paradigm, indicating that the individual capacity to appropriately store energy surplus in the form of fat within the AT determines and prevents the toxic deposition of lipids in other organs, such as the pancreas. Thus, we posit that when the maximal storing capacity of AT is exceeded, individuals will develop T2D. In this review, we provide an insight into mechanisms by which the AT controls pancreas lipid content and homeostasis in case of obesity to offer an adipocentric perspective of pancreatic lipotoxicity in the pathogenesis of diabetes. Moreover, we suggest that improving AT function is a valid therapeutic approach to fighting obesity-associated complications including diabetes.

Open access