Association of increased upper trunk and decreased leg fat with 2-h glucose in control and HIV-infected persons.

ObjectiveChanges in body fat distribution and abnormal glucose metabolism are common in HIV-infected patients. We hypothesized that HIV-infected participants would have a higher prevalence of impaired glucose tolerance (IGT) compared with control subjects.Research design and methodsA total of 491 HIV-infected and 187 control participants from the second examination of the Study of Fat Redistribution and Metabolic Change in HIV Infection (FRAM) underwent glucose tolerance testing (GTT). Multivariable regression was used to identify factors associated with GTT parameters.ResultsThe prevalence of impaired fasting glucose (IFG) (>110 mg/dL) was similar in HIV-infected and control participants (21 vs. 25%, P = 0.23). In those without IFG, the prevalence of IGT was slightly higher in HIV-infected participants compared with control subjects (13.1 vs. 8.2%, P = 0.14) and in HIV+ participants with lipoatrophy versus without (18.1 vs. 11.5%, P = 0.084). Diabetes detected by GTT was rare (HIV subjects 1.3% and control subjects 0%, P = 0.65). Mean 2-h glucose levels were 7.6 mg/dL higher in the HIV-infected participants (P = 0.012). Increased upper trunk subcutaneous adipose tissue (SAT) and decreased leg SAT were associated with 2-h glucose and IGT in both HIV-infected and control participants. Adjusting for adipose tissue reduced the estimated effects of HIV. Exercise, alcohol use, and current tenofovir use were associated with lower 2-h glucose levels in HIV-infected participants.ConclusionsIn HIV infection, increased upper trunk SAT and decreased leg SAT are associated with higher 2-h glucose. These body fat characteristics may identify HIV-infected patients with normal fasting glucose but nonetheless at increased risk for diabetes

Hubungan Asupan Kalsium, Vitamin D, dan Paparan Sinar Matahari dengan Status Gizi pada Balita Usia 3-5 Tahun

The purpose of the study was to analyze the relationship between calcium intake, vitamin D intake, and sun exposure with the nutritional status of children aged 3-5 years. This was an observational study with a cross-sectional design. Thirty-six subjects were selected by consecutive sampling. Nutritional status was categorized based on weight-for-height z-score (WHZ). Food intake was assessed using the semi-quantitative food frequency questionnaire, sun exposure data was determined by the sun exposure questionnaire, and physical activity was obtained through the Early Years Physical Activity Questionnaire. This study showed no significant relationship between calcium intake (p = 0.541), vitamin D intake (p = 0.267), and sun exposure (p = 0.568) with the nutritional status of children aged 3-5 years. Intake of protein, fat, fiber, and physical activity also showed no significant relationship with the nutritional status of children, whereas energy and carbohydrate intake showed a significant relationship with the nutritional status of children. This study showed no significant relationship between calcium intake, vitamin D intake, and sun exposure and the nutritional status of children aged 3-5 years. Tujuan penelitian ini adalah untuk menganalisis hubungan asupan kalsium, vitamin D dan paparan sinar matahari dengan status gizi balita usia 3-5 tahun. Penelitian ini merupakan penelitian observasional dengan desain cross-sectional. Tiga puluh enam subjek dipilih dengan consecutive sampling. Status gizi dikategorikan berdasarkan z-score berat badan menurut tinggi badan (BB/TB). Data asupan diperoleh melalui wawancara dengan instrumen Semi Quantitative Food Frequency Questionnaire. Data paparan matahari didapatkan menggunakan kuesioner paparan sinar matahari, aktivitas fisik diperoleh melalui Early Years Physical Activity Questionnaire. Data dianalisis menggunakan uji Pearson (parametrik) dan Rank-Spearman (non-parametrik). Penelitian ini menunjukkan tidak terdapat hubungan signifikan antara asupan kalsium (p=0,541), asupan vitamin D (p=0,267), dan paparan sinar matahari (p=0,568) dengan status gizi balita usia 3-5 tahun. Asupan protein, lemak, serat, dan aktivitas fisik juga menunjukkan tidak terdapat hubungan signifikan dengan status gizi balita. Sebaliknya asupan energi dan karbohidrat menunjukkan adanya hubungan signifikan dengan status gizi balita. Penelitian ini menunjukkan tidak terdapat hubungan antara asupan kalsium, asupan vitamin D dan paparan sinar matahari dengan status gizi balita usia 3-5 tahun

Cancer associated fibroblasts (CAFs) are activated in cutaneous basal cell carcinoma and in the peritumoural skin

Abstract Background Cutaneous basal cell carcinoma (BCC) is the commonest cancer worldwide. BCC is locally invasive and the surrounding stromal microenvironment is pivotal for tumourigenesis. Cancer associated fibroblasts (CAFs) in the microenvironment are essential for tumour growth in a variety of neoplasms but their role in BCC is poorly understood. Methods Material included facial BCC and control skin from the peritumoural area and from the buttocks. With next-generation sequencing (NGS) we compared mRNA expression between BCC and peritumoural skin. qRT-PCR, immunohistochemical and immunofluorescent staining were performed to validate the NGS results and to investigate CAF-related cyto-and chemokines. Results NGS revealed upregulation of 65 genes in BCC coding for extracellular matrix components pointing at CAF-related matrix remodeling. qRT-PCR showed increased mRNA expression of CAF markers FAP-α, PDGFR-β and prolyl-4-hydroxylase in BCC. Peritumoural skin (but not buttock skin) also exhibited high expression of PDGFR-β and prolyl-4-hydroxylase but not FAP-α. We found a similar pattern for the CAF-associated chemokines CCL17, CCL18, CCL22, CCL25, CXCL12 and IL6 with high expression in BCC and peritumoural skin but absence in buttock skin. Immunofluorescence revealed correlation between FAP-α and PDGFR-β and CXCL12 and CCL17. Conclusion Matrix remodeling is the most prominent molecular feature of BCC. CAFs are present within BCC stroma and associated with increased expression of chemokines involved in tumour progression and immunosuppression (CXCL12, CCL17). Fibroblasts from chronically sun-exposed skin near tumours show gene expression patterns resembling that of CAFs, indicating that stromal fibroblasts in cancer-free surgical BCC margins exhibit a tumour promoting phenotype

Mild cold effects on hunger, food intake, satiety and skin temperature in humans.

BACKGROUND: Mild cold exposure increases energy expenditure and can influence energy balance, but at the same time it does not increase appetite and energy intake. OBJECTIVE: To quantify dermal insulative cold response, we assessed thermal comfort and skin temperatures changes by infrared thermography. METHODS: We exposed healthy volunteers to either a single episode of environmental mild cold or thermoneutrality. We measured hunger sensation and actual free food intake. After a thermoneutral overnight stay, five males and five females were exposed to either 18°C (mild cold) or 24°C (thermoneutrality) for 2.5 h. Metabolic rate, vital signs, skin temperature, blood biochemistry, cold and hunger scores were measured at baseline and for every 30 min during the temperature intervention. This was followed by an ad libitum meal to obtain the actual desired energy intake after cold exposure. RESULTS: We could replicate the cold-induced increase in REE. But no differences were detected in hunger, food intake, or satiety after mild cold exposure compared with thermoneutrality. After long-term cold exposure, high cold sensation scores were reported, which were negatively correlated with thermogenesis. Skin temperature in the sternal area was tightly correlated with the increase in energy expenditure. CONCLUSIONS: It is concluded that short-term mild cold exposure increases energy expenditure without changes in food intake. Mild cold exposure resulted in significant thermal discomfort, which was negatively correlated with the increase in energy expenditure. Moreover, there is a great between-subject variability in cold response. These data provide further insights on cold exposure as an anti-obesity measure.The study was funded by NIHR, BRC Seed Fund, individual grants: ML and MS: Marie Curie Fellowship, CYT: Welcome Trust Fellowship, SV: MRC, BHF and BBSRC, AVP: BBSRC.This is the final version of the article. It first appeared from Bioscientifica via https://doi.org/ 10.1530/EC-16-000

PPAR alpha L162V underlies variation in serum triglycerides and subcutaneous fat volume in young males

Background: Of the five sub-phenotypes defining metabolic syndrome, all are known to have strong genetic components ( typically 50 - 80% of population variation). Studies defining genetic predispositions have typically focused on older populations with metabolic syndrome and/or type 2 diabetes. We hypothesized that the study of younger populations would mitigate many confounding variables, and allow us to better define genetic predisposition loci for metabolic syndrome. Methods: We studied 610 young adult volunteers ( average age 24 yrs) for metabolic syndrome markers, and volumetric MRI of upper arm muscle, bone, and fat pre- and post-unilateral resistance training. Results: We found the PPARa L162V polymorphism to be a strong determinant of serum triglyceride levels in young White males, where carriers of the V allele showed 78% increase in triglycerides relative to L homozygotes ( LL = 116 +/- 11 mg/ dL, LV = 208 +/- 30 mg/ dL; p = 0.004). Men with the V allele showed lower HDL ( LL = 42 +/- 1 mg/ dL, LV = 34 +/- 2 mg/ dL; p = 0.001), but women did not. Subcutaneous fat volume was higher in males carrying the V allele, however, exercise training increased fat volume of the untrained arm in V carriers, while LL genotypes significantly decreased in fat volume ( LL = - 1,707 +/- 21 mm(3), LV = 17,617 +/- 58 mm(3); p = 0.002), indicating a systemic effect of the V allele on adiposity after unilateral training. Our study suggests that the primary effect of PPARa L162V is on serum triglycerides, with downstream effects on adiposity and response to training. Conclusion: Our results on association of PPARa and triglycerides in males showed a much larger effect of the V allele than previously reported in older and less healthy populations. Specifically, we showed the V allele to increase triglycerides by 78% ( p = 0.004), and this single polymorphism accounted for 3.8% of all variation in serum triglycerides in males ( p = 0.0037)

PPARα L162V underlies variation in serum triglycerides and subcutaneous fat volume in young males

<p>Abstract</p> <p>Background</p> <p>Of the five sub-phenotypes defining metabolic syndrome, all are known to have strong genetic components (typically 50–80% of population variation). Studies defining genetic predispositions have typically focused on older populations with metabolic syndrome and/or type 2 diabetes. We hypothesized that the study of younger populations would mitigate many confounding variables, and allow us to better define genetic predisposition loci for metabolic syndrome.</p> <p>Methods</p> <p>We studied 610 young adult volunteers (average age 24 yrs) for metabolic syndrome markers, and volumetric MRI of upper arm muscle, bone, and fat pre- and post-unilateral resistance training.</p> <p>Results</p> <p>We found the PPARα L162V polymorphism to be a strong determinant of serum triglyceride levels in young White males, where carriers of the V allele showed 78% increase in triglycerides relative to L homozygotes (LL = 116 ± 11 mg/dL, LV = 208 ± 30 mg/dL; p = 0.004). Men with the V allele showed lower HDL (LL = 42 ± 1 mg/dL, LV = 34 ± 2 mg/dL; p = 0.001), but women did not. Subcutaneous fat volume was higher in males carrying the V allele, however, exercise training increased fat volume of the untrained arm in V carriers, while LL genotypes significantly decreased in fat volume (LL = -1,707 ± 21 mm³, LV = 17,617 ± 58 mm³; p = 0.002), indicating a systemic effect of the V allele on adiposity after unilateral training. Our study suggests that the primary effect of PPARα L162V is on serum triglycerides, with downstream effects on adiposity and response to training.</p> <p>Conclusion</p> <p>Our results on association of PPARα and triglycerides in males showed a much larger effect of the V allele than previously reported in older and less healthy populations. Specifically, we showed the V allele to increase triglycerides by 78% (p = 0.004), and this single polymorphism accounted for 3.8% of all variation in serum triglycerides in males (p = 0.0037).</p

Psoriatic skin inflammation induces a pre-diabetic phenotype via the endocrine actions of skin secretome

Objective: Psoriasis is a chronic inflammatory skin disease that is thought to affect ∼2% of the global population. Psoriasis has been associated with ∼30% increased risk of developing type 2 diabetes (T2D), with numerous studies reporting that psoriasis is an independent risk-factor for T2D, separate from underlying obesity. Separately, studies of skin-specific transgenic mice have reported altered whole-body glucose homeostasis in these models. These studies imply a direct role for skin inflammation and dysfunction in mediating the onset of T2D in psoriasis patients, potentially via the endocrine effects of the skin secretome on key metabolic tissues. We used a combination of in vivo and ex vivo mouse models and ex vivo human imiquimod (IMQ) models to investigate the effects of psoriasis-mediated changes in the skin secretome on whole-body metabolic function. Methods: To induce psoriatic skin inflammation, mice were topically administered 75 mg of 5% IMQ cream (or Vaseline control) to a shaved dorsal region for 4 consecutive days. On day 5, mice were fasted for glucose and insulin tolerance testing, or sacrificed in the fed state with blood and tissues collected for analysis. To determine effects of the skin secretome, mouse skin was collected at day 5 from IMQ mice and cultured for 24 h. Conditioned media (CM) was collected and used 1:1 with fresh media to treat mouse explant subcutaneous adipose tissue (sAT) and isolated pancreatic islets. For human CM experiments, human skin was exposed to 5% IMQ cream for 20 min, ex vivo, to induce a psoriatic phenotype, then cultured for 24 h. CM was collected, combined 1:1 with fresh media and used to treat human sAT ex vivo. Markers of tissue inflammation and metabolic function were determined by qPCR. Beta cell function in isolated islets was measured by dynamic insulin secretion. Beta-cell proliferation was determined by measurement of Ki67 immunofluorescence histochemistry and BrDU uptake, whilst islet apoptosis was assessed by caspase 3/7 activity. All data is expressed as mean ± SEM. Results: Topical treatment with IMQ induced a psoriatic-like phenotype in mouse skin, evidenced by thickening, erythema and inflammation of the skin. Topical IMQ treatment induced inflammation and signs of metabolic dysfunction in sub-cutaneous and epidydimal adipose tissue, liver, skeletal muscle and gut tissue. However, consistent with islet compensation and a pre-diabetic phenotype, IMQ mice displayed improved glucose tolerance, increased insulin and c-peptide response to glucose, and increased beta cell proliferation. Treatment of sAT with psoriatic mouse or human skin-CM replicated the in vivo phenotype, leading to increased inflammation and metabolic dysfunction in mouse and human sAT. Treatment of pancreatic islets with psoriatic mouse skin-CM induced increases in beta-proliferation and apoptosis, thus partially replicating the in vivo phenotype. Conclusions: Psoriasis-like skin inflammation induces a pre-diabetic phenotype, characterised by tissue inflammation and markers of metabolic dysfunction, together with islet compensation in mice. The in vivo phenotype is partially replicated by exposure of sAT and pancreatic islets to psoriatic-skin conditioned media. These results support the hypothesis that psoriatic skin inflammation, potentially via the endocrine actions of the skin secretome, may constitute a novel pathophysiological pathway mediating the development of T2D

ВЛИЯНИЕ КОРТИЗОЛА И СОМАТОТРОПНОГО ГОРМОНА НА РАЗВИТИЕ ОКСИДАТИВНОГО СТРЕССА У ДЕТЕЙ ПРИ КРИТИЧЕСКИХ СОСТОЯНИЯХ ИНФЕКЦИОННОЙ ПРИРОДЫ

Критические состояния, наблюдающиеся при нейроинфекционных заболеваниях у детей, как правило, сопровождаются значительным дисбалансом гормонов стресса: кортизола, соматотропного гормона (СТГ) и резкими сдвигами процессов свободнорадикального окисления (СРО). Целью нашего исследования было охарактеризовать сдвиги уровня СТГ и кортизола, интенсивности СРО в крови больных детей с нейроинфекциями, находящихся в критических состояниях. Установлены различные изменения уровней кортизола и СТГ в остром периоде у больных в критических состояниях, коррелирующие с уровнем свободнорадикального окисления: достоверная положительная корреляция с уровнем СТГ, отрицательная – с концентрацией кортизола. Резкое снижение уровня кортизола и СРО, низкий уровень СТГ с отсутствием динамики нормализации предполагают неблагоприятное течение нейроинфекционного процесса, и именно эти дети наиболее уязвимы в плане прогноза последствий критических состояний

ВЛИЯНИЕ КОРТИЗОЛА И СОМАТОТРОПНОГО ГОРМОНА НА РАЗВИТИЕ ОКСИДАТИВНОГО СТРЕССА У ДЕТЕЙ ПРИ КРИТИЧЕСКИХ СОСТОЯНИЯХ ИНФЕКЦИОННОЙ ПРИРОДЫ

Критические состояния, наблюдающиеся при нейроинфекционных заболеваниях у детей, как правило, сопровождаются значительным дисбалансом гормонов стресса: кортизола, соматотропного гормона (СТГ) и резкими сдвигами процессов свободнорадикального окисления (СРО). Целью нашего исследования было охарактеризовать сдвиги уровня СТГ и кортизола, интенсивности СРО в крови больных детей с нейроинфекциями, находящихся в критических состояниях. Установлены различные изменения уровней кортизола и СТГ в остром периоде у больных в критических состояниях, коррелирующие с уровнем свободнорадикального окисления: достоверная положительная корреляция с уровнем СТГ, отрицательная – с концентрацией кортизола. Резкое снижение уровня кортизола и СРО, низкий уровень СТГ с отсутствием динамики нормализации предполагают неблагоприятное течение нейроинфекционного процесса, и именно эти дети наиболее уязвимы в плане прогноза последствий критических состояний