Is the Rate of Metabolic Ageing and Survival Determined by Basal Metabolic Rate in the Zebra Finch?

The relationship between energy metabolism and ageing is of great interest because aerobic metabolism is the primary source of reactive oxygen species which is believed to be of major importance in the ageing process. We conducted a longitudinal study on captive zebra finches where we tested the effect of age on basal metabolic rate (BMR), as well as the effect of BMR on the rate of metabolic ageing (decline in BMR with age) and survival. Basal metabolic rate declined with age in both sexes after controlling for the effect of body mass, indicating a loss of functionality with age. This loss of functionality could be due to accumulated oxidative damage, believed to increase with increasing metabolic rate, c.f. the free radical theory of ageing. If so, we would expect the rate of metabolic ageing to increase and survival to decrease with increasing BMR. However, we found no effect of BMR on the rate of metabolic ageing. Furthermore, survival was not affected by BMR in the males. In female zebra finches there was a tendency for survival to decrease with increasing BMR, but the effect did not reach significance (P<0.1). Thus, the effect of BMR on the rate of functional deterioration with age, if any, was not strong enough to influence neither the rate of metabolic ageing nor survival in the zebra finches.     

Metabolic Syndrome and Nephrolithiasis Risk: Should the Medical Management of Nephrolithiasis Include the Treatment of Metabolic Syndrome?

This article reviews the relationship between metabolic syndrome (MetS) and nephrolithiasis, as well as the clinical implications for patients with this dual diagnosis. MetS, estimated to affect 25% of adults in the United States, is associated with a fivefold increase in the risk of developing diabetes, a doubling of the risk of acquiring cardiovascular disease, and an increase in overall mortality. Defined as a syndrome, MetS is recognized clinically by numerous constitutive traits, including abdominal obesity, hypertension, dyslipidemia (elevated triglycerides, low high-density lipoprotein cholesterol), and hyperglycemia. Urologic complications of MetS include a 30% higher risk of nephrolithiasis, with an increased percentage of uric acid nephrolithiasis in the setting of hyperuricemia, hyperuricosuria, low urine pH, and low urinary volume. Current American Urological Association and European Association of Urology guidelines suggest investigating the etiology of nephrolithiasis in affected individuals; however, there is no specific goal of treating MetS as part of the medical management. Weight loss and exercise, the main lifestyle treatments of MetS, counter abdominal obesity and insulin resistance and reduce the incidence of cardiovascular events and the development of diabetes. These recommendations may offer a beneficial adjunctive treatment option for nephrolithiasis complicated by MetS. Although definitive therapeutic recommendations must await further studies, it seems both reasonable and justifiable for the urologist, as part of a multidisciplinary team, to recommend these important lifestyle changes to patients with both conditions. These recommendations should accompany the currently accepted management of nephrolithiasis.Key words: Nephrolithiasis, Metabolic syndrome, Uric acid nephrolithiasisMetabolic syndrome (MetS), as defined by the National Cholesterol Education Program and the Adult Treatment Panel III in 2001 (and updated in 2005), represents a growing medical problem affecting more than 22% of US adults.^1–4 It is associated with an almost fivefold increase in the risk of developing diabetes and a doubling of the risk of acquiring cardiovascular disease.⁵ MetS is a clinical disorder defined by the presence of at least three of the following criteria: central obesity (abdominal girth > 102 cm [40 in] men and > 88 cm [35 in] women), low high-density lipoprotein (HDL) cholesterol (< 40 mg/dL in men and < 50 mg/dL in women), hypertriglyceridemia (> 150 mg/dL), hypertension (blood pressure > 130/85 mm Hg), and elevated fasting glucose (> 100 mg/dL).^2,4 The development of MetS appears to result from a complex interaction of genetics, phenotypic visceral fat accumulation (central obesity), insulin resistance, and sedentary behavior.^5,6 Beyond cardiometabolic risks, MetS has a wide range of long-term complications, including nonalcoholic fatty liver disease, polycystic ovarian syndrome, obstructive sleep apnea, hypogonadism, lipodystrophy, microvascular disease, and chronic renal disease.⁶ An important urologic complication of MetS, not routinely cited, is nephrolithiasis.^6–8Nephrolithiasis continues to be a major cause of morbidity and healthcare spending.⁹ A history of kidney stones is approximately twice as common in individuals with three criteria for MetS and three times as common in those with five criteria for MetS, as compared with those with none.¹⁰ These trends were confirmed in a large-scale, nationwide study of 30,448 Japanese patients with urolithiasis, who demonstrated that MetS was associated with a significantly increased risk of hypercalciuria, hyperuricosuria, hyperoxaluria, and hypocitraturia, independent of age and sex.¹¹ Additionally, patients with a history of nephrolithiasis are significantly more likely to have multiple risk factors for cardiovascular disease, premature atherosclerosis, and cardiovascular events.^10,12,13 It is unknown whether this is primarily a reflection of factors associated with nephrolithiasis, such as obesity, hypertension, or glucose intolerance/diabetes, or due to components of MetS, such as insulin resistance.¹⁴ The current American Urological Association (AUA) guidelines on the medical management of kidney stones suggests a need for future research on advising patients to exercise and lose weight, but does not make definitive recommendations on these lifestyle changes.¹⁵     

Metabolic syndrome in children and adolescents--risk for sleep-disordered breathing and obstructive sleep-apnoea syndrome?

The clinical relevance of the term "metabolic syndrome", the definition criteria, and predictive power are being disputed. Inclusion of sleep-disordered breathing and sleep apnoea into a definition of metabolic syndrome is also controversial once children and/or adolescents are affected. Nevertheless, along with the increasing prevalence of childhood obesity, the prevalence of the metabolic syndrome in obese children is reported at 30%, irrespective of the definition applied. Moreover, childhood obesity is associated with sleep-disordered breathing. Adipocytokines, cytokines secreted from adipose tissue, are thought to play a major role in the pathophysiology of metabolic syndrome. Leptin was initially suggested as a promising "anti-obesity" hormone. New concepts indicate that in humans leptin and its soluble receptor may be more important in states of energy deficiency rather than a predictor of the metabolic syndrome. Adiponectin, on the other hand, is not only related to obesity and insulin resistance, but appears to be the strongest predictor for metabolic syndrome, even in children. In newborns and infants, both adipocytokines occur in high concentrations, even though this cannot completely explain the increased risk for ensuing metabolic disease later in life. Finally, low-grade systemic inflammation may underlie the clustering of metabolic risk factors. Overall factors from the adipose tissue may constitute not only markers but also mediators of metabolic sequelae of obesity.     

Metabolic Engineering for Production of β-Carotene and Lycopene in Saccharomyces cerevisiae

We have engineered a conventional yeast, Saccharomyces cerevisiae, to confer a novel biosynthetic pathway for the production of β-carotene and lycopene by introducing the bacterial carotenoid biosynthesis genes, which are individually surrounded by the promoters and terminators derived from S. cerevisiae. β-Carotene and lycopene accumulated in the cells of this yeast, which was considered to be a result of the carbon flow for the ergosterol biosynthetic pathway being partially directed to the pathway for the carotenoid production.     

Use of Fat-Fed Rats to Study the Metabolic and Vascular Sequelae of Obesity and ��-Adrenergic Antagonism

Obesity-associated cardiovascular disease exerts profound human and monetary costs, creating a mounting need for cost-effective and relevant in vivo models of the complex metabolic and vascular interrelationships of obesity. Obesity is associated with endothelial dysfunction and inflammation. Free fatty acids (FFA), generated partly through β-adrenergic receptor-mediated lipolysis, may impair endothelium-dependent vasodilation (EDV) by proinflammatory mechanisms. β-Adrenergic antagonists protect against cardiovascular events by mechanisms not fully defined. We hypothesized that β antagonists may exert beneficial effects, in part, by inhibiting lipolysis and reducing FFA. Further, we sought to evaluate the fat-fed rat as an in vivo model of obesity-induced inflammation and EDV. Control and fat-fed rats were given vehicle or β antagonist for 28 d. Serum FFA were measured to determine the association to serum IL6, TNFα, and C-reactive protein and to femoral artery EDV. Compared with controls, fat-fed rats weighed more and had higher FFA, triglyceride, leptin, and insulin levels. Unexpectedly, in control and fat-fed rats, β antagonism increased FFA, yet inflammatory cytokines were reduced and EDV was preserved. Therefore, reduction of FFA is unlikely to be the mechanism by which β antagonists protect the endothelium. These results reflect the need for validation of ex vivo models of obesity-induced inflammation and endothelial dysfunction, concurrent with careful control of dietary fat composition and treatment duration.Abbreviations: CRP, C-reactive protein; EDV, endothelium-dependent vasodilation; FFA, free fatty acids; FTI, flow–time integral; L-NAME, N_ω-nitro-L-arginine methyl ester; MAP, mean arterial pressure; PKA, protein kinase AThe prevalence of overweight and obese adults in the United States has increased by almost 20% over the last 3 decades.³⁶ Similar upward trends have been observed in persons between 6 and 19 y of age.³⁷ The obesity epidemic extracts a monetary cost of more than $92 billion on medical care alone⁵⁶ and a profound human price in the form of increased disease³⁵ and higher death rates.⁵⁰Obese adults have a higher risk of morbidity and mortality due to cardiovascular disease.⁵⁷ In health, endothelial cells that line the luminal surface of blood vessels release mediators that facilitate the appropriate regulation of multiple processes, including vascular permeability, inflammation and cell adhesion, coagulation, maintenance of intercellular matrix, lipid metabolism, and vascular reactivity.^25,42 Dysregulation of these processes favors inflammation, coagulation, and vasoconstriction. Not surprisingly, endothelial dysfunction as measured by impairment of endothelium-dependent vasodilation (EDV) is an early and reliable predictor of cardiovascular events in humans.^43,47Obese persons have increased serum free fatty acids (FFA).¹ Obesity^14,53 and FFA¹³ are associated with increased circulating inflammatory markers, specifically IL6, TNFα, and C-reactive protein (CRP). In addition, both obesity³² and FFA^8,46 are associated with impaired EDV, and FFA exert direct adverse inflammatory effects on the endothelium.¹⁸Partly in response to stimulation of β-adrenergic receptors, FFA are the principle moiety secreted from adipocytes. β-Adrenergic antagonist drugs reduce morbidity and mortality in patients with coronary artery disease^9,26 and affect both the myocardium^2,38 and vasculature.^5,51,55 The mechanisms by which β-adrenergic antagonists exert protection remain unclear, but reduced generation of FFA might play a role.The first aim of the present study was to determine whether β antagonism lowers serum FFA in fat-fed rats and whether the magnitude and direction of change in FFA is correlated with circulating inflammatory markers and EDV. The β₁- and β₃-receptor subtypes predominantly mediate lipolysis in rodent adipose;^12,30 however, to minimize the potential for compensatory upregulation of unopposed receptors in this study, the β₁β₂ antagonist propranolol was combined with the β₃ antagonist SR59230A (Sigma-Aldrich, St Louis, MO) to exert antagonism at all 3 receptor subtypes. To test whether the high-fat dietary treatment was associated with a metabolic milieu consistent with obesity, serum triglycerides, leptin, glucose, and insulin concentrations were measured.An inexpensive, valid, and physiologically relevant in vivo system would be valuable for studying the pandemic of obesity³¹ and related endothelial dysfunction.¹⁷ We are unaware of studies of whether long-term high-fat feeding affects in vivo EDV in the rat, although a study validating the use of high-resolution ultrasonography to measure in vivo flow-mediated vasodilation in normal rats was published recently.¹⁷ The second aim of our study was to investigate the fat-fed rat as a model of human diet-induced endothelial dysfunction. To retain the complex metabolic-vascular interplay that occurs in the intact organism, we used in vivo measures of EDV to assess the integrated physiologic response. In humans, the dilator response of peripheral vessels is associated with coronary EDV response.⁴⁸ We studied the rat femoral artery, with the aim of demonstrating changes in vasodilator responses in this easily isolated peripheral vascular bed.     

Metabolic differences inBacillus stearothermophilus grown at 55°C and 37°C

Summary Bacillus stearothermophilus was adapted to grow at 55°C and 37°C in a complex medium with almost equivalent yields in cell mass. In both temperature ranges the maximum specific growth rates (μ_max) were identical. Cellular extracts of this bacterium showed remarkable differences in the activity levels of several enzymes, depending on the respective growth temperature. High activities of glyceraldehyde-3-phosphate dehydrogenase and alcohol dehydrogenase were observed in bacteria from thermophilic cultures (55°C) and the respiratory quotient exceeded 1.0. Under anaerobic conditions at 55°C μ_max was the same as in aerobic cultures. No alcohol dehydrogenase was detected in cells from mesophilic cultures (37°C), however, and the level of glyceraldehyde-3-phosphate dehydrogenase was also extremely low under mesophilic conditions. Succinate dehydrogenase and isocitrate dehydrogenase activity appeared to be higher in bacteria grown at 37°C; the resspiratory quotient was always lower than 1.0. At 37°C, acetoin formation was observed regularly, a fermentation product which was never detected in 55°C-cultures. Under anaerobic conditions at 37°C a very low growth rate was found. When adapted to grow at 37°C or 55°C,B. stearothermophilus is apparently able to use different catabolic systems.     

Metabolism, Pharmacogenetics, and Metabolic Drug–Drug Interactions of Antipsychotic Drugs

1. Antipsychotic drugs are extensively metabolised by cytochrome P450 (CYP) enzymes.2. Dispositions of a number of antipsychotic drugs have been shown to cosegregate with polymorphism of CYP2D6.3. Metabolic drug–drug interactions have frequently been observed when antipsychotics are coadministered with other drugs.4. Many antipsychotic drugs are converted to active metabolites which can contribute to the therapeutic or side effects of the parent drug.5. Information concerning the individual CYP isoenzymes involved in the metabolism of antipsychotic drugs is important for the safe clinical use of this group of drugs.     

Are Elevated Aminotransferases and Decreased Bilirubin Additional Characteristics of the Metabolic Syndrome?

Abnormal liver tests, as well as morphological changes in the liver, are frequent among obese patients. Other frequent disturbances are visceral fat accumulation, insulin resistance, non-insulin-dependent diabetes mellitus (NIDDM), hypertriglyceridemia, and hypertension; these are a set of aberrations known as the metabolic syndrome. In order to investigate a possible relationship between the metabolic syndrome and impaired liver status we examined associations between liver tests, metabolic variables (insulin, glucose, and triglycerids), body composition and nutrition in 1083 men (BMI 28.8–63.8 kg/m²) and 1367 women (BMI 26.7–68.0 kg/m²) in the ongoing intervention study of Swedish Obese Subjects (SOS). Standard biochemical techniques were used to assess liver status and metabolic variables. Lean body mass (LBM) and masses of visceral and subcutaneous adipose tissue (AT) were estimated by means of computed tomography (CT) calibrated anthropometric equations. In both genders aspartate aminotransferase and alanine aminotransferase were, or tended to be, positively correlated to fasting serum insulin, visceral AT (women), and alcohol intake. In women, the aminotransferases were also correlated with fasting blood glucose. In both genders alkaline phosphatase was, or tended to be, positively associated with visceral AT, insulin (women), and glucose. Bilirubin was negatively correlated to insulin and visceral AT in men and women. Additional multivariate analyses indicated that alcohol had less explanatory power than serum insulin for the examined liver tests, especially among women. These results suggest that pathological liver tests in the obese may represent an expression of the metabolic syndrome.     

The Metabolic Syndrome and ECG Detected Left Ventricular Hypertrophy – Influences from IGF-1 and IGF-Binding Protein-1

Background and Aims

The metabolic syndrome (MetS) is associated with an increased risk for left ventricular hypertrophy (LVH) and cardiovascular mortality. The aim of this study was to investigate potential influences from insulin-like growth factor-1 (IGF-1) and IGF binding protein-1 (IGFBP-1) on the relationship between the MetS and LVH, also taking into account the role of physical activity (PA), use of oestrogen and gender.

Methods and Results

In a population-based cross-sectional study of 60-year-old men (n = 1822) and women (n = 2049) participants underwent physical examination and laboratory tests, including electrocardiography (ECG), and completed an extensive questionnaire. Women showed higher levels of IGFBP-1 than men (37.0 vs. 28.0 µg/l, p<0.001), and women with LVH had lower levels of IGFBP-1 than women without LVH (31.0 µg/l vs. 37.0 µg/l, p<0.001). Furthermore, women with low levels of IGFBP-1 had a significantly increased risk of having LVH (crude OR≈2.5). When stratifying for PA and oestrogen, respectively, a weaker association between IGFBP-1 and LVH was demonstrated in physically active men and women, compared to inactive individuals, as well as in women using oestrogen, compared to non-users.

Conclusion

In a representative sample of 60-year-old Swedish men and women, the main findings were higher levels of IGFBP-1 in women than in men; lower levels of IGFBP-1 in women with LVH, compared to women without LVH; and an increased risk of having LVH in women with low levels of IGFBP-1. The association between IGFBP-1 and LVH was diminished in physically active men and women, as well as in women using oestrogen.     

Characterisation of Gut Microbiota in Ossabaw and G?ttingen Minipigs as Models of Obesity and Metabolic Syndrome

Background

Recent evidence suggests that the gut microbiota is an important contributing factor to obesity and obesity related metabolic disorders, known as the metabolic syndrome. The aim of this study was to characterise the intestinal microbiota in two pig models of obesity namely Göttingen minipigs and the Ossabaw minipigs.

Methods and Findings

The cecal, ileal and colonic microbiota from lean and obese Osabaw and Göttingen minipigs were investigated by Illumina-based sequencing and by high throughput qPCR, targeting the 16S rRNA gene in different phylogenetic groups of bacteria. The weight gain through the study was significant in obese Göttingen and Ossabaw minipigs. The lean Göttingen minipigs’ cecal microbiota contained significantly higher abundance of Firmicutes (P<0.006), Akkermensia (P<0.01) and Methanovibribacter (P<0.01) than obese Göttingen minipigs. The obese Göttingen cecum had higher abundances of the phyla Spirochaetes (P<0.03), Tenericutes (P<0.004), Verrucomicrobia (P<0.005) and the genus Bacteroides (P<0.001) compared to lean minipigs. The relative proportion of Clostridium cluster XIV was 7.6-fold higher in cecal microbiota of obese Göttingen minipigs as compared to lean. Obese Ossabaw minipigs had a higher abundance of Firmicutes in terminal ileum and lower abundance of Bacteroidetes in colon than lean Ossabaw minipigs (P<0.01). Obese Ossabaws had significantly lower abundances of the genera Prevotella and Lactobacillus and higher abundance of Clostridium in their colon than the lean Ossabaws. Overall, the Göttingen and Ossabaw minipigs displayed different microbial communities in response to diet-induced obesity in the different sections of their intestine.

Conclusion

Obesity-related changes in the composition of the gut microbiota were found in lean versus obese Göttingen and Ossabaw minipigs. In both pig models diet seems to be the defining factor that shapes the gut microbiota as observed by changes in different bacteria divisions between lean and obese minipigs.     

Metabolic and Genetic Diversity of Mesophilic and Thermophilic Bacteria Isolated from Composted Municipal Sludge on Poly-ε-caprolactones

Thirty mesophilic and thermophilic bacteria were isolated from thermobiotically digested sewage sludge in culture medium supplemented with poly-ε-caprolactone (PCL). The ability of each purified isolate to degrade PCL and to produce polymer-degrading extracellular enzymes was assessed. Isolates were characterized based on random amplified polymorphic DNA (RAPD), 16S rDNA sequence-based phylogenetic affiliation and carbohydrate-based nutritional versatility. Mesophilic isolates with ability to degrade PCL were attributed to the genera Acinetobacter, Burkholderia, Pseudomonas, and Staphylococcus. Thermophilic isolates were members of the genus Bacillus. Despite the restricted phylogenetic and genotypic diversity observed for thermophiles, their metabolic versatility and wide range of growth temperatures suggest an important activity of these organisms during the whole composting process.     

Metabolic Syndrome and Stroke Recurrence in Chinese Ischemic Stroke Patients – The ACROSS-China Study

Objective

Metabolic syndrome has emerged as a novel risk factor in cardiovascular disease due to its potential for predicting stroke in population-based studies. We investigated the relationship of metabolic syndrome with stroke recurrence.

Methods

This was a retrospective analysis of Chinese patients enrolled in the prospective Abnormal gluCose Regulation in patients with acute strOke acroSS China (ACROSS-China) study after their first ischemic stroke. Metabolic syndrome was defined using the International Diabetes Federation (IDF) criteria. Vascular risk factors were assessed. Outcome was defined as recurrence of stroke within one year after the index ischemic stroke. Cox proportional hazards regression was performed to identify potential predictors of stroke recurrence.

Results

The prevalence of metabolic syndrome among 2639 ischemic stroke patients was 51.35%. During the one-year follow-up, 195 strokes (7.4%) recurred. The multivariate hazard ratio (95% CI) of stroke recurrence was 1.94 (1.39–2.73) for metabolic syndrome. After adjustment for components, metabolic syndrome lost its association with stroke recurrence; in this model, high fasting plasma glucose (IDF definition) was a predictor for stroke recurrence.

Conclusion

Metabolic syndrome may not be predictive for stroke recurrence beyond its component individual factors for Chinese ischemic stroke patients.     

Carbon–Nitrogen Interaction Modulates Plant Growth and Expression of Metabolic Genes in Rice

Carbon (C) and nitrogen (N) interact to coordinate their metabolism in achieving C:N homeostasis in all cellular organisms. Plant shoots and roots take up C and N, respectively, and the coordinated C and N assimilation is essential for normal plant growth and development. In this study, rice was used as a model system for the investigation of molecular mechanisms underlying C–N interactions and coordination in cereal species. We investigated the growth response of rice seedlings to a wide range of exogenous C:N availabilities and established balanced exogenous C:N that was optimal for rice seedling growth. To assess correlations between the modulation of plant growth and the regulation of metabolic gene expression by C:N availabilities, we examined the expression of PEPC, PK, NR, GS, and GOGAT in rice seedlings treated with four C:N availabilities: low C/low N, low C/high N, high C/low N, and high C/high N. It was found that their expression was subjected to complex regulation by C:N availabilities. Our results demonstrate that growth of shoot and root rice seedlings is regulated by C–N interaction and growth modulations are associated with changes in metabolic gene expression. Our findings suggest that rice is a useful model system for the investigation of regulation mechanisms responsible for C–N interaction and coordination in plants.     

Lipoic acid and diabetes—Part III: Metabolic role of acetyl dihydrolipoic acid

Rat liver lipoyl transacetylase catalyzes the formation of acetyl dihydrolipoic acid from acetyl coenzyme A and dihydrolipoic acid. In an earlier paper the formation of acetyl dihydrolipoic from pyruvate and dihydrolipoic acid catalyzed by pyruvate dehydrogenase has been reported. Acetyl dihydrolipoic acid is a substrate for citrate synthase, acetyl coenzyme A carboxylase and fatty acid synthetase. The V_max. for citrate synthase with acetyl dihydrolipoic acid was identical to acetyl coenzyme A (approximately 1 μmol citrate formed/min/mg protein) while the apparent K_m was approximately 4 times higher with acetyl dihydrolipoic acid as the substrate. This may be due to the fact that synthetic acetyl dihydrolipoic acid is a mixture of 4 possible isomers and only one of them may be the substrate for the enzymatic reaction. While dihydrolipoic acid can replace coenzyme A in the activation of succinate catalyzed by succinyl coenzyme A synthetase, the transfer of coenzyme A between succinate and acetoacetyl dihydrolipoic acid catalyzed by succinyl coenzyme A: 3 oxo-acid coenzyme A transferase does not occur.     

RETRACTION: C-reactive Protein and Metabolic Syndrome in Youth: A Strong Relationship?

Retraction: Note from the Editor‐in‐Chief: This paper is retracted Objective: Metabolic syndrome (MS) is on the rise in youth. As high‐sensitivity C‐reactive protein (hs‐CRP) is associated with cardiovascular/metabolic disorders, we evaluated the association between MS and its components and hs‐CRP in a sample of Brazilian overweight and obese youth. Methods and Procedures: A total of 407 students (229 girls, 273 with excessive weight, 11.3 ± 3.2 years) were evaluated. Measurement included BMI, waist circumference (WC), blood pressure, lipids, insulin, and hs‐CRP. Excessive weight was defined using BMI z ‐score; MS by the modified National Cholesterol Education Program—Adult Treatment Panel III. Results: Subjects were classified into two groups: with MS (n = 72) and without (n = 335). hs‐CRP means and medians were higher in MS group (1.41 mg/l vs. 1.06 mg/l, P < 0.001; 2.21 mg/l vs. 1.23 mg/l, P < 0.001). Associations between hs‐CRP quartiles and insulin resistance (IR) (P < 0.001), MS (P < 0.001), WC (P < 0.000), BMI z‐score (P < 0.001), hypertension (P < 0.001), hypertriglyceridemia (P < 0.001), and low HDL‐c (P = 0.023) were significant; adjustment of hs‐CRP for BMI z‐score eliminated the previous association, except for the number of MS components (nMSc) (P < 0.001). Adjusting for homeostasis model assessment method of IR (HOMA‐IR) did not eliminate the relation between hs‐CRP and MS components. Furthermore, increases in BMI z ‐score and nMSc were associated with an increased hs‐CRP. Excessive weight (odds ratio (OR), 7.9; confidence interval (CI), 4.7–13.4; P = 0.000), hypertension (OR, 2.3; CI, 1.3–4.2; P = 0.003), and hypertriglyceridemia (OR, 2.3; CI, 1.5–3.7; P < 0.001) were independently associated with hs‐CRP. Discussion: In youth, hs‐CRP is strongly related with MS and its components, and is also determined by the body composition. This association indicates a precocious proinflammatory state.     

Metabolic theory or metabolic models?

The metabolic theory of ecology (MTE) claims to derive ecological relationships from the structure of resource distribution networks, which is assumed to determine the scaling of metabolism with body mass, and from the effect of temperature on the rate of biological processes. MTE is controversial. I propose that some of the controversy stems from the implicit adoption of different views of science by the proponents and critics of MTE. The perspective of proponents is consistent with the theory-centric view of science called the received view, whereas many of the critics implicitly adopt an alternative view consistent with a model-centric view of science. I propose that adopting the model-centric view can help to settle some of the differences among proponents and critics of MTE.     

γδ T Cells Are Reduced and Rendered Unresponsive by Hyperglycemia and Chronic TNFα in Mouse Models of Obesity and Metabolic Disease

Epithelial cells provide an initial line of defense against damage and pathogens in barrier tissues such as the skin; however this balance is disrupted in obesity and metabolic disease. Skin γδ T cells recognize epithelial damage, and release cytokines and growth factors that facilitate wound repair. We report here that hyperglycemia results in impaired skin γδ T cell proliferation due to altered STAT5 signaling, ultimately resulting in half the number of γδ T cells populating the epidermis. Skin γδ T cells that overcome this hyperglycemic state are unresponsive to epithelial cell damage due to chronic inflammatory mediators, including TNFα. Cytokine and growth factor production at the site of tissue damage was partially restored by administering neutralizing TNFα antibodies in vivo. Thus, metabolic disease negatively impacts homeostasis and functionality of skin γδ T cells, rendering host defense mechanisms vulnerable to injury and infection.