２型糖尿病とメタボリックシンドローム予防のための生活習慣

Visceral fat accumulation plays a central role in the onset and progression of type ２ diabetes and metabolic syndrome. It has been pointed out that Japanese are more likely to have visceral fat accumulation even if their BMI is less than２５kg/m２. Lifestyle-related interventions aimed at weight loss significantly reduce the onset of type ２ diabetes and metabolic syndrome. Visceral fat is characterized by a tendency to decrease from an early stage of weight loss, and a decrease in visceral fat can be expected by a few percent weight loss. It has been reported that weight loss of ３ to ５％ from the current body weight improves hyperglycemia, dyslipidemia, high blood pressure, hyperuricemia, and NAFLD, which are the components of metabolic syndrome. The diet is required to maintain adequate total energy intake, limit energy ratio of lipid, and reduce the amount of saturated fatty acids. In addition to exercising, increasing daily physical activity and reducing sedentary time are also effective for weight loss. The preventive effect of metabolic syndrome can be obtained by combining short-term exercises even if they are not continuous. On the other hand, it is known that being low body weight in the elderly person increase the risk of death. Until middle and old age, prevention of obesity is important because metabolic syndrome consisting of hypernutrition and obesity causes lifestyle-related diseases such as diabetes and dyslipidemia, increasing the risk of death. Since weight loss can reduce skeletal muscle mass as well as fat mass in the elderly, it is important to take measures against undernutrition so as not to limit energy intake too much. Furthermore, in the elderly, it is necessary to combine multiple types of exercise not only to prevent metabolic syndrome and diabetes, but also to prevent sarcopenia and frailty

is equine disease comparable to what we know in humans?

This review summarizes similarities and differences between the metabolic syndromes in humans and equines, concerning the anatomy, symptoms, and pathophysiological mechanisms. In particular, it discusses the structure and distribution of adipose tissue and its specific metabolic pathways. Furthermore, this article provides insights and focuses on issues concerning laminitis in horses and cardiovascular diseases in humans, as well as their overlap

Phosphoprotein enriched in astrocytes (PEA)-15 is a novel regulator of adipose tissue expansion

Acknowledgements P.J.V. was funded by a British Heart Foundation Ph.D. scholarship (FS/16/25/32136). This work was also sup- ported by the Medical Research Council (MR/L002620/1 to J.J.R.), the Biotechnology and Biological Sciences Research Council (BB/K017772/1 to J.J.R.), Diabetes UK (18/0005884 to J.J.R.) and the British Heart Foundation (PG/14/43/30889 to M.D.). The authors gratefully acknowledge the Microscopy and Histology core facility and the Medical Research Facility, University of Aberdeen for their support and assistance in this work.Peer reviewedPublisher PD

Tissue and circulating microRNAs as biomarkers of response to obesity treatment strategies

Background: Obesity, characterized by an increased amount of adipose tissue, is a metabolic chronic alteration which has reached pandemic proportion. Lifestyle changes are the first line therapy for obesity and a large variety of dietary approaches have demonstrated efficacy in promoting weight loss and improving obesity-related metabolic alterations. Besides diet and physical activity, bariatric surgery might be an effective therapeutic strategy for morbid obese patients. Response to weight-loss interventions is characterised by high inter-individual variability, which might involve epigenetic factors. microRNAs have critical roles in metabolic processes and their dysregulated expression has been reported in obesity. Aim: The aim of this review is to provide a comprehensive overview of current studies evaluating changes in microRNA expression in obese patients undergoing lifestyle interventions or bariatric surgery. Results: A considerable number of studies have reported a differential expression of circulating microRNAs before and after various dietary and bariatric surgery approaches, identifying several candidate biomarkers of response to weight loss. Significant changes in microRNA expression have been observed at a tissue level as well, with entirely different patterns between visceral and subcutaneous adipose tissue. Interestingly, relevant differences in microRNA expression have emerged between responders and non-responders to dietary or surgical interventions. A wide variety of dysregulated microRNA target pathways have also been identified, helping to understand the pathophysiological mechanisms underlying obesity and obesity-related metabolic diseases. Conclusions: Although further research is needed to draw firm conclusions, there is increasing evidence about microRNAs as potential biomarkers for weight loss and response to intervention strategies in obesity

A Novel Partial Agonist of the A 1 -Adenosine Receptor and Evidence of Receptor Homogeneity in Adipocytes

ABSTRACT This study characterizes the receptor binding and functional effects of 2R)-2-hydroxycyclopentyl)-amino]purin-9-yl}(4S,5S,2R,3R)-5-[(2-fluorophenylthio)methyl]-oxolane-3,4-diol], a novel N 6 -5Ј-substituted adenosine analog and A 1 -adenosine receptor (A 1 AdoR) agonist, on rat epididymal and inguinal adipocytes and on the isolated heart and compares these effects with those caused by the full agonist N 6 -cyclopentyladenosine (CPA). In addition, the hypothesis that adipocyte A 1 AdoR are a heterogeneous population with regard to their affinities for ligands was tested. CVT-3619 was 10 -100-fold selective for A 1 AdoR versus other AdoR and bound to adipocyte membranes with high (K H ϭ 14 nM) and low (K L ϭ 5.4 M) affinities. CVT-3619 reduced cyclic AMP content and release of nonesterified fatty acids from epididymal adipocytes with IC 50 values of 6 and 44 nM, respectively. CVT-3619 was a partial agonist relative to CPA to reduce lipolysis in epididymal and inguinal adipocytes. CVT-3619 did not change atrial rate in rat heart and caused a small (6-ms) prolongation of the stimulus-to-His bundle interval without causing atrioventricular block in guinea pig heart (effects mediated by A 1 AdoR), whereas CPA caused atrioventricular block and near cessation of atrial electrical activity. CVT-3619 increased coronary conductance (effect mediated by A 2A AdoR) only at concentrations Ն10 M. Rat epididymal adipocyte A 1 AdoR had similar affinities for the antagonist 8-cyclopentyl-1,3-dipropylxanthine in the presence of three dissimilar A 1 AdoR agonists (2-chloro-N 6 -cyclopentyladenosine, N 6 -sulfophenyladenosine, and N-5Ј-ethylcarboxamidoadenosine) as determined by Schild analysis. It was concluded that rat epididymal adipocyte A 1 AdoR are a homogeneous receptor population with regard to affinities for ligands and that CVT-3619 is a partial agonist with selectivity for A 1 AdoR and inhibition of lipolysis

Circannual Patterns of Adipose Tissue Characteristics in a Hibernator, the Thirteen-lined Ground Squirrel (Ictidomys tridecemlineatus)

Obligate hibernators express circannual patterns of body mass and hibernation, which persist under constant laboratory conditions. I hypothesized that in the 13-lined ground squirrel (Ictidomys tridecemlineatus) thermogenic brown adipose tissue (BAT) and lipid storing white adipose tissue (WAT) volume would follow a circannual pattern. I housed animals at either 25°C (thermoneutral) or 5°C with 12h L:12h D photoperiods for an entire year. I determined volume and water-fat ratio of WAT and BAT using magnetic resonance imaging (MRI). BAT volume follows a circannual pattern in both conditions, increasing prior to winter, decreasing in late winter with no change in water-fat ratio. Both body mass and WAT volume of cold-housed animals declined throughout the winter and recovered after hibernation. By contrast, thermoneutral housing produced no circannual pattern in body mass even though WAT volume declined in late winter. Warm-housed animals never entered torpor indicating that they might not be obligate hibernators

Effects of gp130 cytokines on adipocytes

Members of the gp130 cytokine family are known for their pleiotropic roles in various cell types. Our work has focused on their actions in adipocytes. CNTF administration has been shown to ameliorate most complications associated with obesity and type 2 diabetes through an unknown mechanism. In this study CNTF is shown to activate JAK/STAT and MAPK signaling, both in vitro and in vivo. In 3T3-L1 adipocytes, chronic CNTF also regulates the expression of SREBP-1, FAS, IRS-1 and GLUT4. Acute CNTF administration enhances the activation of IRS-1 and Akt by insulin. Our data also demonstrate that the expression of CNTF-specific receptor, CNTFRalpha, is decreased during adipocyte differentiation, but that this protein is expressed in several other tissues, and the level of CNTFRalpha glycosylation varies between different tissues. Most importantly, the expression of CNTFRalpha is dramatically increased in the fat pads of obese and diabetic animals. Even though CT-1 is mostly known for its actions in cardiomyocytes, the work presented demonstrates that, in fat cells, CT-1 can potently induce JAK/STAT and MAPK signaling. Neither CT-1 nor CNTF affected adipocyte differentiation, but chronic CT-1 did induce a decrease in FAS and IRS-1 protein expression. Both CNTF and CT-1 also induced a transient increase in SOCS-3 and a transient decrease in PPARgamma mRNA levels, in a MAPK-independent manner. Our studies also demonstrate that several gp130 cytokines, namely CT-1, LIF and OSM, have the ability to block signaling by other gp130 cytokines, but not GH. These cytokines can also dramatically reduce the half-life of LIFR protein in adipocytes, and this change in LIFR stability correlates with the ability of CT-1, LIF and OSM, to block subsequent gp130 cytokine signaling. The loss of LIFR protein can be prevented by the lysosome inhibitors leupeptin and chloroquine, but not by proteasome inhibitors. In summary, these studies demonstrate than gp130 cytokines have a wide spectrum of effects on both cultured and native adipocytes, and that their actions may be important in various aspects of adipocyte physiology

Condition cardiorespiratoire et profil métabolique : importance du tissu adipeux viscéral

Le présent projet de recherche a été réalisé dans le but d'évaluer la contribution du tissu adipeux viscéral dans la relation entre la condition cardiorespiratoire (CCR) et certains paramètres du syndrome métabolique Les travaux réalisés ont permis d'évaluer la relation entre la condition cardiorespiratoire, le tissu adipeux viscéral et le profil de risque cardiométabolique dans un groupe de femme d'âge moyen. Il a été démontré que les femmes caractérisées par une faible CCR avaient significativement plus de tissu adipeux viscéral que celles caractérisées par une CCR élevée ainsi qu'un profil métabolique plus détérioré. Toutefois, après appariement sur la base de l'accumulation de tissu adipeux viscéral, plus aucune différence significative n'était observée au sein des femmes caractérisées par une CCR faible ou élevée. En somme, ces travaux suggèrent que l'accumulation de tissu adipeux viscéral pourrait être un élément central expliquant les liens entre la capacité cardiorespiratoire et les éléments du syndrome métabolique

Modulation of adipocyte genes by signal transducers and activators of transcription

Members of the STAT transcription factor family are expressed in adipocytes, including STATs 1, 3, 5A, 5B, and 6. Although STATs 1 and 5 proteins are known to be induced during adipogenesis, the functions of these STATs in mature adipocytes are not known. Hence we have sought to identify adipocyte genes which are transcriptionally regulated by STATs to elucidate a role of these proteins in fat cells. We have characterized STAT binding sites in the promoters of four adipocyte genes, PPARγ2, LPL, FAS and C/EBPδ. PPARγ2 expression decreases in adipocytes following exposure to IFNγ, an activator of STAT1. IFNγ induces the binding of STAT1 to a site in the PPARγ2 promoter. Furthermore, the STAT1 binding site is required for IFNγ regulation of the PPARγ2 promoter in vitro. Although CT-1 and LIF induced STAT1 binding to the PPARγ2 promoter, only CT-1 substantially modulated expression of PPARγ2. We have also identified a STAT1 binding site in the promoter of LPL, which is bound by STAT1 following treatment of 3T3-L1 adipocytes with IFNγ. In addition, LPL protein levels are downregulated by IFNγ treatment. Treatment with PRL, an activator of STAT5A, decreased levels of FAS protein and mRNA in adipocytes. Regulation of the rat FAS promoter by PRL required a region of the promoter which contained a STAT5 binding site. Binding to this site by STAT5A was activated by PRL treatment and was highly specific. Finally, in our analysis on the effects of LIF on adipocytes, we determined that the expression SOCS3 and C/EBPδ mRNA transiently increases following treatment of adipocytes with LIF. We identified three STAT1 binding sites within the C/EBPδ promoter, which we hypothesize mediate the induction of C/EBPδ by LIF. Although LIF did not profoundly affect adipogenesis or basal and insulin-stimulated glucose uptake, chronic treatment with LIF abrogated the level of SREBP1 and FAS proteins. In summary, our studies suggest that STAT1 and STAT5 serve to limit synthesis of lipids in mature fat cells, limiting expansion of adipocytes and accretion of adipose tissue. The identification of PPARγ, FAS, and LPL as STAT-regulated genes provides insight into the molecular mechanisms of energy homeostasis, adipocyte physiology and the action of cytokines in fat

The impact of obesity and inflammation on metabolic risk factors for cardiovascular disease and type two diabetes in black and white South African women

[T]he overall aim of this thesis was to investigate the ethnic-specific role of inflammation in obesity and related metabolic risk factors associated with T2DM and CVD in apparently healthy black and white premenopausal South African women