Zinc deficiency in Chronic Kidney Disease: Is there a Relationship with Adipose Tissue and Atherosclerosis?

Cardiovascular complications caused by an accelerated atherosclerotic disease consist the major cause of morbidity and mortality in patients with chronic kidney disease (CKD). These patients present multiple atherosclerotic risk factors, considered traditional, as well as nontraditional risk factors such as inflammation and oxidative stress. These complications are also seen in obesity, in which endothelial dysfunction is one of the early stages of atherosclerosis. The impact of trace metal deficiencies on this process is not well studied in patients with CKD and in obese people, although the influence of trace elements depletion, particularly zinc (Zn), may have significant clinical implications. This brief review describes the functions of Zn as well as the respective role of this trace element in atherosclerosis processes, with a particular emphasis on obese patients with chronic kidney disease.     

Does a High‐protein Diet Improve Weight Loss in Overweight and Obese Children?

Objective: To evaluate the effect of a high‐protein diet on anthropometry, body composition, subjective appetite, and mood sensations in overweight and obese children attending a residential weight‐loss camp. Research Methods and Procedures: Children (120; BMI, 33.1 ± 5.5 kg/m²; age, 14.2 ± 1.9 years) were randomly assigned to either a standard or high‐protein diet group (15% vs. 22.5% protein, respectively). All children were assessed at baseline and at the end of the camp for anthropometry, body composition, blood pressure, biochemical variables (n = 27), and subjective appetite and mood sensations (n = 50). Results: Attendance at the weight‐loss camp resulted in significant improvements in most measures. Campers lost 5.5 ± 2.9 kg in body weight (p < 0.001) and 3.8 ± 5.4 kg in fat mass (p < 0.001) and reduced their BMI standard deviation score by 0.27 ± 0.1 (p < 0.001) and their waist circumference by 6.6 ± 2.8 cm (p < 0.001). Subjective sensations of hunger increased significantly over the camp duration, but no other changes in appetite or mood were observed. There were no significant differences between the two diets on any physical or subjective measures. Discussion: Weight‐loss camps are effective in assisting children to lose weight and improve on a range of health outcomes, independently of the protein content of the diet. The implications of an increase in hunger associated with weight loss needs to be considered. Further work is warranted to investigate whether higher levels of dietary protein are feasible or effective in longer‐term weight‐loss interventions of this type.     

Is the Prevalence of Successful Weight Loss and Maintenance Higher in the General Community than the Research Clinic?

BARTLETT, SUSAN J., MYLES S. FAITH, KEVIN R. FONTAINE, LAWRENCE J. CHESKIN, AND DAVID B. ALLISON. Is the prevalence of successful weight loss and maintenance higher in the general community than the research clinic? Obes Res. Objective: The prevalence of successful weight loss remains unclear. In 1982, Schachter concluded that in the general population, the rate of “self-cured” obesity approached 63%–much higher than the rate from clinical trials. Several subsequent studies have addressed this issue. Research Methods and Procedures: Our initial goal was to meta-analyze these studies to evaluate the validity of the original hypotheses and the extent to which additional investigations supported the findings. We began by restating Schachter's hypotheses in precise, testable terms. Results: A systematic review of these studies found many methodological limitations and much heterogeneity among the samples studied, hypotheses addressed, and operational definitions. Some of these limitations appear to stem from the lack of clear, precise statements of the exact hypotheses tested. Differences among studies are delineated, and we outline why meta-analytic pooling of these data appears inappropriate. Conclusions: The current data are inadequate to draw any definite conclusions regarding the cure rate of obesity. Criteria for the adequate study of success rates with “self-cure” in the general population are proposed.     

Expression of Obesity Markers and Persistent Organic Pollutants Levels in Adipose Tissue of Obese Patients: Reinforcing the Obesogen Hypothesis?

Introduction

Persistent Organic Pollutants (POPs) accumulate in adipose tissue and some are described to possess endocrine disrupting capacities. Therefore, it is important to evaluate their effects on key endocrine pathways in adipose tissue (AT), to further evaluate their potential role in metabolic pathologies such as obesity.

Objectives

The aim is twofold: (i) evaluate gene expression levels of obesity marker genes, i.e. the adipokines leptin (LEP), adiponectin (ADIPOQ) and Tumor Necrosis Factor α (TNFα) and the nuclear receptor, Peroxisome Proliferator Activated Receptor γ (PPARγ) in paired subcutaneous (SAT) and visceral (VAT) AT of obese subjects (n = 50) and to relate these values to serum concentrations of LEP and ADIPOQ (ii) evaluate the association of expression levels of marker genes in AT and serum with POP concentrations in AT.

Results and Conclusions

Leptin and adiponectin levels in serum were positively correlated to respectively expression levels of leptin in SAT and adiponectin in VAT. Our study shows more significant correlations between gene expression of obesity marker genes and POP concentrations in VAT compared to SAT. Since VAT is more important than SAT in pathologies associated with obesity, this suggests that POPs are able to influence the association between obesity and the development of associated pathologies. Moreover, this finding reveals the importance of VAT when investigating the obesogen hypothesis. Concerning PPARγ expression in VAT, negative correlations with polychlorinated biphenyls (PCBs) concentrations were found in non T2D patients. LEP serum concentrations correlated with several PCBs in women whereas in men no correlations were found. This strengthens the potential importance of gender differences in obesity and within the obesogen hypothesis.     

Physical Activity and Low-Fat Diet: Is it Enough to Maintain Weight Stability in the Reduced-Obese Individual Following Weight Loss by Drug Therapy and Energy Restriction?

DOUCET, ERIC, PASCAL IMBEAULT, NATALIE ALMÉRAS, AND ANGELO TREMBLAY. Physical activity and low-fat diet: Is it enough to maintain weight stability in the reduced-obese individual following weight loss by drug therapy and energy restriction? Obes Res. Objective: The anthropometric and physiological effects of a physical activity (PA) and a mildly energy-restricted low-fat diet (LFD) follow-up program after a long-term dietary restriction were studied in 12 men and 8 women. Research Methods and Procedures: The dietary restriction (?700 kcal/day) was accompanied by a fenfluramine (60 mg/day) or placebo treatment for 15 weeks, whereas the mean duration of the PA-LFD follow-up was 18 weeks. Results: The long-term dietary restriction reduced body weight (?11. 9 and ?7. 6 kg, p<. 001), fat mass (FM) (?10. 6 and ?5. 8 kg, p<0. 01), resting metabolic rate (RMR) (?304 kcal/day, p<0. 01 and ?148 kcal/day, NS) in men and women, respectively. A decrease in fat-free mass (FFM) was also observed in women (?1. 8 kg, p<0. 05). The PA-LFD follow-up preserved weight stability at a reduced body weight and caused an additional significant decrease in FM for men (?3. 4 kg, p<0. 05). This part of the intervention also caused an increase in daily RMR for men (134 kcal/day, NS) to the point where this value no longer differed from the pre-energy restriction value. In contrast, RMR was further reduced in women (?200 kcal/day) to the point where it Significantly differed from initial values (p<0. 01). Resting seated heart rate was reduced by the PA-LFD follow-up in men leading it to differ significantly from both pre- and post-energy restriction values (?8. 5 and ?5. 5 bpm, p<0. 01). Discussion: In conclusion, these results suggest that a PA-LFD follow-up has the potential to permit body weight stability and may even accentuate fat loss in the reduced-obese state. Moreover, resting energy expenditure is increased under such conditions in men. These stimulating effects seem to be specific to energy metabolism since seated heart rate was either further reduced or remained stable in response to the PA-LFD follow-up.     

Chemokine Expression in Inflamed Adipose Tissue Is Mainly Mediated by NF-κB

Immune cell infiltration of expanding adipose tissue during obesity and its role in insulin resistance has been described and involves chemokines. However, studies so far have focused on a single chemokine or its receptor (especially CCL2 and CCL5) whereas redundant functions of chemokines have been described. The objective of this work was to explore the expression of chemokines in inflamed adipose tissue in obesity. Human and mouse adipocytes were analyzed for expression of chemokines in response to inflammatory signal (TNF-α) using microarrays and gene set enrichment analysis. Gene expression was verified by qRT-PCR. Chemokine protein was determined in culture medium with ELISA. Chemokine expression was investigated in human subcutaneous adipose tissue biopsies and mechanism of chemokine expression was investigated using chemical inhibitors and cellular and animal transgenic models. Chemokine encoding genes were the most responsive genes in TNF-α treated human and mouse adipocytes. mRNA and protein of 34 chemokine genes were induced in a dose-dependent manner in the culture system. Furthermore, expression of those chemokines was elevated in human obese adipose tissue. Finally, chemokine expression was reduced by NF-κB inactivation and elevated by NF-κB activation. Our data indicate that besides CCL2 and CCL5, numerous other chemokines such as CCL19 are expressed by adipocytes under obesity-associated chronic inflammation. Their expression is regulated predominantly by NF-κB. Those chemokines could be involved in the initiation of infiltration of leukocytes into obese adipose tissue.     

Is It Possible to Detect Activated Brown Adipose Tissue in Humans Using Single-Time-Point Infrared Thermography under Thermoneutral Conditions? Impact of BMI and Subcutaneous Adipose Tissue Thickness

Purpose

To evaluate the feasibility to detect activated brown adipose tissue (BAT) using single-time-point infrared thermography of the supraclavicular skin region under thermoneutral conditions. To this end, infrared thermography was compared with 18-F-FDG PET, the current reference standard for the detection of activated BAT.

Methods

120 patients were enrolled in this study. After exclusion of 18 patients, 102 patients (44 female, 58 male, mean age 58±17 years) were included for final analysis. All patients underwent a clinically indicated 18F-FDG-PET/CT examination. Immediately prior to tracer injection skin temperatures of the supraclavicular, presternal and jugular regions were measured using spatially resolved infrared thermography at room temperature. The presence of activated BAT was determined in PET by typical FDG uptake within the supraclavicular adipose tissue compartments. Local thickness of supraclavicular subcutaneous adipose tissue (SCAT) was measured on CT. Measured skin temperatures were statistically correlated with the presence of activated BAT and anthropometric data.

Results

Activated BAT was detected in 9 of 102 patients (8.8%). Local skin temperature of the supraclavicular region was significantly higher in individuals with active BAT compared to individuals without active BAT. However, after statistical correction for the influence of BMI, no predictive value of activated BAT on skin temperature of the supraclavicular region could be observed. Supraclavicular skin temperature was significantly negatively correlated with supraclavicular SCAT thickness.

Conclusion

We conclude that supraclavicular SCAT thickness influences supraclavicular skin temperature and thus makes a specific detection of activated BAT using single-time-point thermography difficult. Further studies are necessary to evaluate the possibility of BAT detection using alternative thermographic methods, e.g. dynamic thermography or MR-based thermometry taking into account BMI as a confounding factor.     

Is the Outgrowth of Transplant-Derived Axons Guided by Host Astrocytes and Myelin Loss?

Loss of cortical neurons may lead to sever and sometimes irreversible deficits in motor function in a number of neuropathological conditions. Absence of spontaneous axonal regeneration following trauma in the adult central nervous system (CNS) is attributed to inhibitory factors associated to the CNS white matter and to the non-permissive environment provided by reactive astrocytes that form a physical and biochemical barrier scar. Neural transplantation of embryonic neurons has been widely assessed as a potential approach to overcome the generally limited capacity of the mature CNS to regenerate axons or to generate new neurons in response to cell loss. We have recently shown that embryonic (E14) mouse motor cortical tissue transplanted into the damaged motor cortex of adult mice developed efferent projections to appropriate cortical and subcortical host targets including distant areas such as the spinal cord, with a topographical organization similar to that of intact motor cortex. Several parameters might account for the outgrowth of axonal projections from embryonic neurons within a presumably non-permissive adult brain, among which are astroglial reactions and myelin formation. In the present study, we have examined the role of astrocytes and myelin in the axonal outgrowth of transplanted neurons.Key Words: motor cortex, neuronal transplantation, embryonic cells, GFP, GFAP, PLP     

PEDF Expression Is Inhibited by Insulin Treatment in Adipose Tissue via Suppressing 11β-HSD1

Early intensive insulin therapy improves insulin sensitivity in type 2 diabetic patients; while the underlying mechanism remains largely unknown. Pigment epithelium-derived factor (PEDF), an anti-angiogenic factor, is believed to be involved in the pathogenesis of insulin resistance. Here, we hypothesize that PEDF might be down regulated by insulin and then lead to the improved insulin resistance in type 2 diabetic patients during insulin therapy. We addressed this issue by investigating insulin regulation of PEDF expression in diabetic conditions. The results showed that serum PEDF was reduced by 15% in newly diagnosed type 2 diabetic patients after insulin therapy. In adipose tissue of diabetic Sprague-Dawley rats, PEDF expression was associated with TNF-α elevation and it could be decreased both in serum and in adipose tissue by insulin treatment. In adipocytes, PEDF was induced by TNF-α through activation of NF-κB. The response was inhibited by knockdown and enhanced by over expression of NF-κB p65. However, PEDF expression was indirectly, not directly, induced by NF-κB which promoted 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) expression in adipocytes. 11β-HSD1 is likely to stimulate PEDF expression through production of active form of glucocorticoids as dexamethasone induced PEDF expression in adipose tissue. Insulin inhibited PEDF by down-regulating 11β-HSD1 expression. The results suggest that PEDF activity is induced by inflammation and decreased by insulin through targeting 11β-HSD1/glucocorticoid pathway in adipose tissue of diabetic patients.     

Does Obesity Modify the Relationship between Exposure to Occupational Factors and Musculoskeletal Pain in Men? Results from the GAZEL Cohort Study

Objective

To analyze relationships between physical occupational exposures, post-retirement shoulder/knee pain, and obesity.

Methods

9 415 male participants (aged 63–73 in 2012) from the French GAZEL cohort answered self-administered questionnaires in 2006 and 2012. Occupational exposures retrospectively assessed in 2006 included arm elevation and squatting (never, <10 years, ≥10 years). “Severe” shoulder and knee pain were defined as ≥5 on an 8-point scale. BMI was self-reported.

Results

Mean BMI was 26.59 kg/m² +/−3.5 in 2012. Long-term occupational exposure to arm elevation and squatting predicted severe shoulder and knee pain after retirement. Obesity (BMI≥30 kg/m²) was a risk factor for severe shoulder pain (adjusted OR 1.28; 95% CI 1.03, 1.90). Overweight (adjusted OR 1.71; 1.28,2.29) and obesity (adjusted OR 3.21; 1.90,5.41) were risk factors for severe knee pain. In stratified models, associations between long-term squatting and severe knee pain varied by BMI.

Conclusion

Obesity plays a role in relationships between occupational exposures and musculoskeletal pain. Further prospective studies should use BMI in analyses of musculoskeletal pain and occupational factors, and continue to clarify this relationship.     

Is the Outgrowth of Transplant-Derived Axons Guided by Host Astrocytes and Myelin Loss?

Loss of cortical neurons may lead to sever and sometimes irreversible deficits in motor function in a number of neuropathological conditions. Absence of spontaneous axonal regeneration following trauma in the adult central nervous system (CNS) is attributed to inhibitory factors associated to the CNS white matter and to the non-permissive environment provided by reactive astrocytes that form a physical and biochemical barrier scar. Neural transplantation of embryonic neurons has been widely assessed as a potential approach to overcome the generally limited capacity of the mature CNS to regenerate axons or to generate new neurons in response to cell loss. We have recently shown that embryonic (E14) mouse motor cortical tissue transplanted into the damaged motor cortex of adult mice developed efferent projections to appropriate cortical and subcortical host targets including distant areas such as the spinal cord, with a topographical organization similar to that of intact motor cortex. Several parameters might account for the outgrowth of axonal projections from embryonic neurons within a presumably non-permissive adult brain, among which are astroglial reactions and myelin formation. In the present study, we have examined the role of astrocytes and myelin in the axonal outgrowth of transplanted neurons.     

Does the Method of Weight Loss Effect Long-Term Changes in Weight,Body Composition or Chronic Disease Risk Factors in Overweight or Obese Adults? A Systematic Review

Background

Differences in biological changes from weight loss by energy restriction and/or exercise may be associated with differences in long-term weight loss/regain.

Objective

To assess the effect of weight loss method on long-term changes in weight, body composition and chronic disease risk factors.

Data Sources

PubMed and Embase were searched (January 1990-October 2013) for studies with data on the effect of energy restriction, exercise (aerobic and resistance) on long-term weight loss. Twenty articles were included in this review.

Study Eligibility Criteria

Primary source, peer reviewed randomized trials published in English with an active weight loss period of >6 months, or active weight loss with a follow-up period of any duration, conducted in overweight or obese adults were included.

Study Appraisal and Synthesis Methods

Considerable heterogeneity across trials existed for important study parameters, therefore a meta-analysis was considered inappropriate. Results were synthesized and grouped by comparisons (e.g. diet vs. aerobic exercise, diet vs. diet + aerobic exercise etc.) and study design (long-term or weight loss/follow-up).

Results

Forty percent of trials reported significantly greater long-term weight loss with diet compared with aerobic exercise, while results for differences in weight regain were inconclusive. Diet+aerobic exercise resulted in significantly greater weight loss than diet alone in 50% of trials. However, weight regain (∼55% of loss) was similar in diet and diet+aerobic exercise groups. Fat-free mass tended to be preserved when interventions included exercise.     

Does Clinical Depression Affect the Accuracy of Self‐reported Height and Weight in Obese Women?

Objective: Recent research from a self‐report survey showed a strong association between obesity and clinical depression in women. The present analysis assessed whether differential bias in self‐reports of height and weight as a function of depression influences the apparent strength of the association. Methods: Accuracy of self‐reported height and weight was assessed in 250 obese (mean BMI=38.7 kg/m²) women, 135 of whom met the American Psychiatric Association DSM‐IV diagnostic criteria for clinical depression. Results: Depressed and non‐depressed women underreported their weight by 1.5 and 1.2 kg, respectively. They underreported their height by 0.002 and 0.003 m, respectively. Discussion: Bias in self‐reports of body weight and height is similar in depressed and non‐depressed obese women. The underreporting of weight in both groups is similar in magnitude to that seen in normal weight women. Thus, using self‐reports of height and weight seems unlikely to bias estimates of the association between obesity and clinical depression in women.     

The Potential Crosstalk Between the Brain and Visceral Adipose Tissue in Alzheimer’s Development

Neurochemical Research - The bidirectional communication between the brain and peripheral organs have been widely documented, but the impact of visceral adipose tissue (VAT) dysfunction and its...     

Is Adipose Tissue a Reservoir for Viral Spread,Immune Activation,and Cytokine Amplification in Coronavirus Disease 2019?

Coronavirus disease 2019 (COVID‐19), the worst pandemic in more than a century, has claimed >125,000 lives worldwide to date. Emerging predictors for poor outcomes include advanced age, male sex, preexisting cardiovascular disease, and risk factors including hypertension, diabetes, and, more recently, obesity. This article posits new obesity‐driven predictors of poor COVID‐19 outcomes, over and above the more obvious extant risks associated with obesity, including cardiometabolic disease and hypoventilation syndrome in intensive care patients. This article also outlines a theoretical mechanistic framework whereby adipose tissue in individuals with obesity may act as a reservoir for more extensive viral spread, with increased shedding, immune activation, and cytokine amplification. This paper proposes studies to test this reservoir concept with a focus on specific cytokine pathways that might be amplified in individuals with obesity and COVID‐19. Finally, this paper underscores emerging therapeutic strategies that might benefit subsets of patients in which cytokine amplification is excessive and potentially fatal.     

Is the Relationship between Body Size and Trophic Niche Position Time-Invariant in a Predatory Fish? First Stable Isotope Evidence

Characterizing relationships between individual body size and trophic niche position is essential for understanding how population and food-web dynamics are mediated by size-dependent trophic interactions. However, whether (and how) intraspecific size-trophic relationships (i.e., trophic ontogeny pattern at the population level) vary with time remains poorly understood. Using archival specimens of a freshwater predatory fish Gymnogobius isaza (Tanaka 1916) from Lake Biwa, Japan, we assembled a long-term (>40 years) time-series of the size-dependence of trophic niche position by examining nitrogen stable isotope ratios (δ ¹⁵N) of the fish specimens. The size-dependence of trophic niche position was defined as the slope of the relationship between δ ¹⁵N and log body size. Our analyses showed that the slope was significantly positive in about 60% of years and null in other years, changing through time. This is the first quantitative (i.e., stable isotope) evidence of long-term variability in the size-trophic relationship in a predatory fish. This finding had implications for the fish trophic dynamics, despite that about 60% of the yearly values were not statistically different from the long-term average. We proposed hypotheses for the underlying mechanism of the time-varying size-trophic relationship.     

Interleukin-1β Regulates Fat-Liver Crosstalk in Obesity by Auto-Paracrine Modulation of Adipose Tissue Inflammation and Expandability

The inflammasome has been recently implicated in obesity-associated dys-metabolism. However, of its products, the specific role of IL-1β was clinically demonstrated to mediate only the pancreatic beta-cell demise, and in mice mainly the intra-hepatic manifestations of obesity. Yet, it remains largely unknown if IL-1β, a cytokine believed to mainly function locally, could regulate dysfunctional inter-organ crosstalk in obesity. Here we show that High-fat-fed (HFF) mice exhibited a preferential increase of IL-1β in portal compared to systemic blood. Moreover, portally-drained mesenteric fat transplantation from IL-1βKO donors resulted in lower pyruvate-glucose flux compared to mice receiving wild-type (WT) transplant. These results raised a putative endocrine function for visceral fat-derived IL-1β in regulating hepatic gluconeogenic flux. IL-1βKO mice on HFF exhibited only a minor or no increase in adipose expression of pro-inflammatory genes (including macrophage M1 markers), Mac2-positive crown-like structures and CD11b-F4/80-double-positive macrophages, all of which were markedly increased in WT-HFF mice. Further consistent with autocrine/paracrine functions of IL-1β within adipose tissue, adipose tissue macrophage lipid content was increased in WT-HFF mice, but significantly less in IL-1βKO mice. Ex-vivo, adipose explants co-cultured with primary hepatocytes from WT or IL-1-receptor (IL-1RI)-KO mice suggested only a minor direct effect of adipose-derived IL-1β on hepatocyte insulin resistance. Importantly, although IL-1βKOs gained weight similarly to WT-HFF, they had larger fat depots with similar degree of adipocyte hypertrophy. Furthermore, adipogenesis genes and markers (pparg, cepba, fabp4, glut4) that were decreased by HFF in WT, were paradoxically elevated in IL-1βKO-HFF mice. These local alterations in adipose tissue inflammation and expansion correlated with a lower liver size, less hepatic steatosis, and preserved insulin sensitivity. Collectively, we demonstrate that by promoting adipose inflammation and limiting fat tissue expandability, IL-1β supports ectopic fat accumulation in hepatocytes and adipose-tissue macrophages, contributing to impaired fat-liver crosstalk in nutritional obesity.