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Fernandez-Real J.M.,University of Girona | Fernandez-Real J.M.,CIBER ISCIII | Fernandez-Real J.M.,Institute Dinvestigacio Biomedica Of Girona Idibgi | Pickup J.C.,Diabetes Research Group
Diabetologia | Year: 2012

In this edition of 'Then and now' the initial studies by J.C. Pickup and colleagues supporting the hypothesis that type 2 diabetes is caused by activated innate immunity, published in Diabetologia in 1997 (40:1286-1292), are discussed. These initial findings led to research that has uncovered links between insulin resistance, obesity, circulating immune markers, immunogenetic susceptibility, macrophage function and chronic infection. Genetic variations leading to the altered production or function of circulating innate immune proteins, cellular pattern recognition receptors and inflammatory cytokines are linked to obesity, insulin resistance and type 2 diabetes. Components of the innate immune system in the muscle, bone, liver and adipose tissue, as well as macrophages, have been revealed to play a role in systemic insulin action. Evolutionary pressures, such as acute infections at the population level (pandemics) and chronic low exposure to environmental products or infectious agents, may have contributed to increased susceptibility and to the current increase in the prevalence of insulin resistance and type 2 diabetes. © 2011 Springer-Verlag. Source

Ortega F.J.,Institute Dinvestigacio Biomedica Of Girona Idibgi | Ortega F.J.,CIBER ISCIII | Fernandez-Real J.M.,Institute Dinvestigacio Biomedica Of Girona Idibgi | Fernandez-Real J.M.,CIBER ISCIII
Hormone and Metabolic Research | Year: 2013

Recent findings in adipose tissue (AT) have uncovered negative interactions among obesity, lipogenesis, and fatty acid (FA) storage, perhaps in response to the increased production of proinflammatory cytokines and transcription factors. Emerging evidence highlights that local hypoxia, generation of reactive oxygen and nitrogen species, increased immune cells infiltration and activation, senescence, inflammation, energy consumption, and decreased lipogenesis in the AT are interrelated and may lead to impaired cytokine and hormonal secretion by adipocytes, and ectopic fat deposition in obesity that strengths the increased risk of suffering metabolic disorders in obese subjects. The information summarized in this review attempts to defend the interdependent relationship of these proofs of concept, supporting the idea that inflamed and dysfunctional AT are synonymous when referring to obesity. This may happen in severe obese subjects with a large and long-lasting fat excess, when fat depots have reached the point in which excessive fat storage, cell density, and diminished oxygen availability promote decreased lipo/adipogenesis and increased lipolysis and FA release. This response may be induced by an important inflammatory component that promotes angiogenesis and insulin resistance, but also by leptin and the increase of T3 in hyperplastic AT. © 2013 Georg Thieme Verlag KG Stuttgart New York. Source

Moreno-Navarrete J.M.,Institute Dinvestigacio Biomedica Of Girona Idibgi | Fernandez-Real J.M.,Institute Dinvestigacio Biomedica Of Girona Idibgi
Expert Review of Clinical Immunology | Year: 2014

Currently, obesity-associated metabolic disturbances are envisioned as chronic inflammatory processes, characterized by activation of both innate and adaptive immunity. Although the features of chronic inflammation in obese subjects are clearly defined, the signals and mechanisms that trigger chronic inflammation are not well understood. Recent studies suggest an imbalance in circulating antimicrobial proteins as a possible cause of obesity-associated metabolic disturbances and insulin resistance. This imbalance promotes a relative failure in the capacity of buffering external insults and might cause the onset of chronic inflammation and immunologic alterations in obesity. Here, we review the current literature on the possible role of circulating antimicrobial proteins in obesity-associated immunologic alterations. © 2014 Informa UK, Ltd. Source

Jove M.,Institute Of Recerca Biomedica Of Lleida Irblleida Udl | Moreno-Navarrete J.M.,Institute Dinvestigacio Biomedica Of Girona Idibgi | Pamplona R.,Institute Of Recerca Biomedica Of Lleida Irblleida Udl | Ricart W.,Institute Dinvestigacio Biomedica Of Girona Idibgi | And 2 more authors.
FASEB Journal | Year: 2014

Despite their differential effects on human metabolic pathophysiology, the differences in omental and subcutaneous lipidomes are largely unknown. To explore this field, liquid chromatography coupled with mass spectrometry was used for lipidome analyses of adipose tissue samples (visceral and subcutaneous) selected from a group of obese subjects (n=38). Transcriptomics and in vitro studies in adipocytes were used to confirm the pathways affected by location. The analyses revealed the existence of obesityrelated specific lipidome signatures in each of these locations, attributed to selective enrichment of specific triglycerides, glycerophospholipids, and sphingolipids, because these were not observed in adipose tissues from nonobese individuals. The changes were compatible with subcutaneous enrichment in pathways involved in adipogenesis, triacylglyceride synthesis, and lipid droplet formation, as well as increased β-oxidation. Marked differences between omental and subcutaneous depots in obese individuals were seen in the association of lipid species with metabolic traits (body mass index and insulin sensitivity). Targeted studies also revealed increased cholesterol (Δ56%) and cholesterol epoxide (Δ34%) concentrations in omental adipose tissue. In view of the effects of cholesterol epoxide, which induced enhanced expression of adipocyte differentiation and β-oxidation genes in human omental adipocytes, a novel role for cholesterol epoxide as a signaling molecule for differentiation is proposed. In summary, in obesity, adipose tissue exhibits a locationspecific differential lipid profile that may contribute to explaining part of its distinct pathogenic role. © FASEB. Source

Ortega F.J.,Institute Dinvestigacio Biomedica Of Girona Idibgi | Moreno-Navarrete J.M.,Institute Dinvestigacio Biomedica Of Girona Idibgi | Pardo G.,Institute Dinvestigacio Biomedica Of Girona Idibgi | Sabater M.,Institute Dinvestigacio Biomedica Of Girona Idibgi | And 7 more authors.
PLoS ONE | Year: 2010

Background: Potential regulators of adipogenesis include microRNAs (miRNAs), small non-coding RNAs that have been recently shown related to adiposity and differentially expressed in fat depots. However, to date no study is available, to our knowledge, regarding miRNAs expression profile during human adipogenesis. Thereby, the aim of this study was to investigate whether miRNA pattern in human fat cells and subcutaneous adipose tissue is associated to obesity and comorbidities and whether miRNA expression profile in adipocytes is linked to adipogenesis. Methodology/Principal Findings:We performed a global miRNA expression microarray of 723 human and 76 viral mature miRNAs in human adipocytes during differentiation and in subcutaneous fat samples from non-obese (n = 6) and obese with (n = 9) and without (n = 13) Type-2 Diabetes Mellitus (DM-2) women. Changes in adipogenesis-related miRNAs were then validated by RT-PCR. Fifty of 799 miRNAs (6.2%) significantly differed between fat cells from lean and obese subjects. Seventy miRNAs (8.8%) were highly and significantly up or down-regulated in mature adipocytes as compared to preadipocytes. Otherwise, 17 of these 799 miRNAs (2.1%) were correlated with anthropometrical (BMI) and/or metabolic (fasting glucose and/or triglycerides) parameters. We identified 11 miRNAs (1.4%) significantly deregulated in subcutaneous fat from obese subjects with and without DM-2. Interestingly, most of these changes were associated with miRNAs also significantly deregulated during adipocyte differentiation. Conclusions/Significance:The remarkable inverse miRNA profile revealed for human pre-adipocytes and mature adipocytes hints at a closely crosstalk between miRNAs and adipogenesis. Such candidates may represent biomarkers and therapeutic targets for obesity and obesity-related complications. © 2010 Ortega et al. Source

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