Wnt10b knockdown regulates the relative balance of adipose tissue-resident T cells and inhibits white fat deposition.

BACKGROUND: Wnt10b is one of critical Wnt family members that being involved in networks controlling stemness, pluripotency and cell fate decisions. However, its role in adipose-resident T lymphocytes and further in fat metabolism yet remains largely unknown. METHODS AND RESULTS: In the present study, we demonstrated a distinctive effect for Wnt10b on the relative balance of T lymphocytes in adipose tissue by using a Wnt10b knockdown mouse model. Wnt10b knockdown led to a reduction of adipose-resident CD4+ T cells and an elevation of Foxp3+/CD4+ Treg cells. Wnt10b-knockdown mice fed with standard diet showed less white fat deposition owing to the suppressed adipogenic process. Moreover, under high fat diet conditions, Wnt10b knockdown resulted in an alleviated obesity symptoms, as well as an improvement of glucose homeostasis and hepatic steatosis. CONCLUSIONS: Collectively, we reveal an unexpected and novel function for Wnt10b in mediating the frequency of adipose-resident T cell subsets, that when knockdown skewing toward a Treg-dominated phenotype and further improving fat metabolism.

Adipose-Derived Stem Cells: Angiogenetic Potential and Utility in Tissue Engineering.

Adipose tissue (AT) is a large and important energy storage organ as well as an endocrine organ with a critical role in many processes. Additionally, AT is an enormous and easily accessible source of multipotent cell types used in our day for all types of tissue regeneration. The ability of adipose-derived stem cells (ADSCs) to differentiate into other types of cells, such as endothelial cells (ECs), vascular smooth muscle cells, or cardiomyocytes, is used in tissue engineering in order to promote/stimulate the process of angiogenesis. Being a key for future successful clinical applications, functional vascular networks in engineered tissue are targeted by numerous in vivo and ex vivo studies. The article reviews the angiogenic potential of ADSCs and explores their capacity in the field of tissue engineering (TE).

H3K27ac modification and transcription characteristics of adipose and muscle tissues in Chuxiang Black pig.

The establishment of high-quality pork breeds for improving meat quality in the pig industry is needed. The Chuxiang Black (CX) pig is a new breed developed from Chinese local pigs and Western lean pigs that has a high proportion of lean meat and excellent meat quality. However, the characteristics of cis-regulatory elements in CX pigs are still unknown. In this study, cis-regulatory elements of muscle and adipose tissues in CX pigs were investigated using ChIP-seq and RNA sequencing. Compared with the reported cis-regulatory elements of muscle and adipose tissues, 1768 and 1012 highly activated enhancers and 433 and 275 highly activated promoters in CX muscle and adipose tissues were identified, respectively. Motif analysis showed that transcription factors, such as MEF2A and MEF2C, were core regulators of highly activated enhancers and promoters in muscle. Similarly, the transcription factors JUNB and CUX1 were identified as essential for highly activated enhancers and promoters in CX adipose tissue. These results enrich the resources for the analysis of cis-regulatory elements in the pig genome and provide new basic data for further meat quality improvement through breeding in pigs.

Adipose Tissue in Cardiovascular Disease: From Basic Science to Clinical Translation.

The perception of adipose tissue as a metabolically quiescent tissue, primarily responsible for lipid storage and energy balance (with some endocrine, thermogenic, and insulation functions), has changed. It is now accepted that adipose tissue is a crucial regulator of metabolic health, maintaining bidirectional communication with other organs including the cardiovascular system. Additionally, adipose tissue depots are functionally and morphologically heterogeneous, acting not only as sources of bioactive molecules that regulate the physiological functioning of the vasculature and myocardium but also as biosensors of the paracrine and endocrine signals arising from these tissues. In this way, adipose tissue undergoes phenotypic switching in response to vascular and/or myocardial signals (proinflammatory, profibrotic, prolipolytic), a process that novel imaging technologies are able to visualize and quantify with implications for clinical prognosis. Furthermore, a range of therapeutic modalities have emerged targeting adipose tissue metabolism and altering its secretome, potentially benefiting those at risk of cardiovascular disease.

Adipose tissue as a therapeutic target for vascular damage in Alzheimer's disease.

Adipose tissue has recently been recognized as an important endocrine organ that plays a crucial role in energy metabolism and in the immune response in many metabolic tissues. With this regard, emerging evidence indicates that an important crosstalk exists between the adipose tissue and the brain. However, the contribution of adipose tissue to the development of age-related diseases, including Alzheimer's disease, remains poorly defined. New studies suggest that the adipose tissue modulates brain function through a range of endogenous biologically active factors known as adipokines, which can cross the blood-brain barrier to reach the target areas in the brain or to regulate the function of the blood-brain barrier. In this review, we discuss the effects of several adipokines on the physiology of the blood-brain barrier, their contribution to the development of Alzheimer's disease and their therapeutic potential. LINKED ARTICLES: This article is part of a themed issue From Alzheimer's Disease to Vascular Dementia: Different Roads Leading to Cognitive Decline. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v181.6/issuetoc.

Comprehensive analyses of circulating cardiometabolic proteins and objective measures of fat mass.

BACKGROUND: The underlying molecular pathways for the effect of excess fat mass on cardiometabolic diseases is not well understood. Since body mass index is a suboptimal measure of body fat content, we investigated the relationship of fat mass measured by dual-energy X-ray absorptiometry with circulating cardiometabolic proteins. METHODS: We used data from a population-based cohort of 4950 Swedish women (55-85 years), divided into discovery and replication samples; 276 proteins were assessed with three Olink Proseek Multiplex panels. We used random forest to identify the most relevant biomarker candidates related to fat mass index (FMI), multivariable linear regression to further investigate the associations between FMI characteristics and circulating proteins adjusted for potential confounders, and principal component analysis (PCA) for the detection of common covariance patterns among the proteins. RESULTS: Total FMI was associated with 66 proteins following adjustment for multiple testing in discovery and replication multivariable analyses. Five proteins not previously associated with body size were associated with either lower FMI (calsyntenin-2 (CLSTN2), kallikrein-10 (KLK10)), or higher FMI (scavenger receptor cysteine-rich domain-containing group B protein (SSC4D), trem-like transcript 2 protein (TLT-2), and interleukin-6 receptor subunit alpha (IL-6RA)). PCA provided an efficient summary of the main variation in FMI-related circulating proteins involved in glucose and lipid metabolism, appetite regulation, adipocyte differentiation, immune response and inflammation. Similar patterns were observed for regional fat mass measures. CONCLUSIONS: This is the first large study showing associations between fat mass and circulating cardiometabolic proteins. Proteins not previously linked to body size are implicated in modulation of postsynaptic signals, inflammation, and carcinogenesis.

Epicardial adipose tissue and cardiac lipotoxicity: A review.

Epicardial adipose tissue (EAT) has morphological and physiological contiguity with the myocardium and coronary arteries, making it a visceral fat deposit with some unique properties. Under normal circumstances, EAT exhibits biochemical, mechanical, and thermogenic cardioprotective characteristics. Under clinical processes, epicardial fat can directly impact the heart and coronary arteries by secreting proinflammatory cytokines via vasocrine or paracrine mechanisms. It is still not apparent what factors affect this equilibrium. Returning epicardial fat to its physiological purpose may be possible by enhanced local vascularization, weight loss, and focused pharmacological therapies. This review centers on EAT's developing physiological and pathophysiological dimensions and its various and pioneering clinical utilities.

A systems approach to evaluate nitrogen utilization efficiency and environmental impacts of swine growing-finishing feeding programs in U.S. pork production systems.

Traditionally, swine diets have been formulated to meet nutrient requirements at the lowest cost with little regard toward minimizing environmental impacts. The overall objective of this study was to evaluate the relative differences among four grower-finisher feeding programs, using precision diet formulation practices, on growth performance, carcass composition, nitrogen utilization efficiency, and environmental impacts. In experiment 1, four 4-phase growing-finishing feeding programs consisting of diets containing corn and soybean meal (CSBM), low protein CSBM supplemented with crystalline amino acids (LP), CSBM with 30% distillers dried grains with solubles (DDGS), and DDGS supplemented with crystalline Ile, Val, and Trp (DDGS + IVT) were fed to 288 mixed sex pigs (initial body weight [BW] = 36.9 ±â€…4.2 kg) for 12 wk to determine effects on growth performance and carcass characteristics. Pigs fed with CSBM had greater (P < 0.05) final BW than those fed with LP and DDGS, and greater gain efficiency than pigs fed with LP. Pigs fed with DDGS + IVT tended to have greater (P = 0.06) backfat depth than pigs fed with DDGS, and less (P < 0.05) loin muscle area than pigs fed with CSBM. In experiment 2, nitrogen (N) and phosphorus (P) balance of barrows (n = 32; initial BW = 59.9 ±â€…5.1 kg) fed with each of the phase-2 diets from experiment 1 was determined in a 12-d metabolism study (7 d adaptation and 5 d collection). Pigs fed with CSBM had a greater (P < 0.05) amount of N retained than pigs fed with other diets, but also had a greater (P < 0.05) amount of urinary N excretion and blood urea N than pigs fed with LP and DDGS + IVT diets. Pigs fed with LP tended (P = 0.07) to have the greatest N utilization efficiency but the least (P < 0.05) P retained as a percentage of P intake among dietary treatments. Diet composition and data collected from experiments 1 and 2 were used to calculate life cycle assessment environmental impacts using Opteinics software (BASF, Lampertheim, Germany). The CSBM feeding program had the least impact on climate change, marine and freshwater eutrophication, and fossil resource use. The LP feeding program had the least impact on acidification, terrestrial eutrophication, and water use, while the DDGS feeding programs had the least impact on land use. These results indicate that feeding CSBM diets optimized growth performance and carcass composition while simultaneously reducing impacts on climate change, marine and freshwater eutrophication, and fossil resource use compared with the other feeding programs evaluated.

Developing and evaluating feeding programs that optimize growth performance and carcass composition, while minimizing cost, nutrient excretion in manure, and environmental impact is essential for achieving sustainable pork production systems. Four growing-finishing feeding programs consisting of typical corn-soybean meal (CSBM) diets, low protein CSBM diets containing supplemental crystalline amino acids (LP), CSBM diets containing 30% corn dried distillers grains with solubles (DDGS), and DDGS diets containing supplemental crystalline Ile, Val, and Trp were evaluated to compare their effects on growth performance, carcass composition, nitrogen and phosphorus utilization efficiency, and several environmental impact measures. Pigs fed CSBM diets had greater final body weight than those fed the LP and DDGS diets, and greater gain efficiency than pigs fed the LP diets, but there were no differences in the percentage of carcass lean among feeding programs. However, pigs fed the LP diets had the greatest nitrogen utilization efficiency and the least impact on acidification, terrestrial eutrophication, and water use among these feeding programs. The CSBM feeding program had the least impact on climate change, marine and freshwater eutrophication, and fossil resource use, while the DDGS feeding programs had the least impact on land use.

Strain-dependent shear properties of human adipose tissue in vivo.

INTRODUCTION: Human adipose tissue (fat) deforms substantially under normal physiological loading and during impact. Thus, accurate data on strain-dependent stiffness of fat is essential for the creation of accurate biomechanical models. Previous studies on ex vivo samples reported human fat to be nonlinear and viscoelastic. When static compression is combined with magnetic resonance (MR) elastography (an imaging technique used to measure viscoelasticity in vivo), the large deformation properties of tissues can be determined. Here, we use magnetic resonance elastography to quantify fat shear modulus in vivo under increasing compressive strain and compare it to the underlying passive gluteal muscle. METHODS: The right buttocks of ten female participants were incrementally compressed at four levels while MR elastography (50 Hz) and mDixon images were acquired. Maps of tissue shear modulus (G*) were reconstructed from the MR elastography phase images. Tissue strain was estimated from registration of deformed and undeformed mDixon images. Linear mixed models were fit to the natural logarithm of the compressive strain and shear modulus data for each tissue. RESULTS: Shear modulus increased in an exponential relationship with compressive strain in fat: Gfat*=748.5*Cyy-1.18Pa, and to a lesser extent in muscle: Gmuscle*=956.4*Cyy-0.36Pa. The baseline (undeformed) stiffness of fat was significantly lower than that of muscle (mean G*fat = 752 Pa, mean G*muscle = 1000 Pa, paired samples t-test, t = -4.24, p = 0.001). However, fat exhibited a significantly higher degree of strain dependence (characterised by the exponent of the curve, t = -6.47, p = 0.0001). CONCLUSION: Static compression of human adipose tissue results in an increase in apparent viscoelastic shear modulus (stiffness), in an exponentially increasing relationship. The relationships defined here can be used in the development of physiologically realistic computational models for impact, injury and biomechanical modelling.

Fit-Fat Index is better associated with heart rate variability compared to fitness and fatness alone as indicators of cardiometabolic human health.

OBJECTIVES: Cardiorespiratory fitness and fatness indicators have been related to heart rate variability (HRV) parameters. The Fit-Fat Index (FFI) is a single index combining cardiorespiratory fitness and fatness indicators. To the best of our knowledge, no studies have previously analyzed whether FFI are related to cardiac autonomic nervous system activity assessed through HRV parameters. This study aimed (i) to examine the association of cardiorespiratory fitness, fatness indicators, and FFI with HRV parameters; and (ii) to report what of the different fatness indicators included in FFI is better associated with HRV parameters in sedentary adults. METHODS: One hundred and fifty healthy adults (74 women; 76 men), aged between 18 and 65 years old, participated in this cross-sectional study. We measured cardiorespiratory fitness (maximal oxygen consumption) and fatness indicators (waist-to-height ratio [WHR], fat mass percentage [FM%] and visceral adipose tissue [VAT]). Three FFIs were calculated as the quotient between cardiorespiratory fitness and one out of three possible fatness indicators: Fit-Fat Index calculated waist-to-height ratio (FFIWHR ), Fit-Fat Index calculated with FM% (FFIFM% ), and Fit-Fat Index calculated with VAT (FFIVAT ). HRV parameters were measured in resting conditions using a Polar RS800CX. RESULTS: FFIWTHR , FFIFM% and FFIVAT were related to different HRV parameters (ß ranges between -0.507 and 0.529; R2 ranges between 0.096 and 0.275; all p < .001) and the association was stronger with HRV parameters than the isolated fitness or fatness indicators (ß ranges between -0.483 and 0.518; R2 ranges between 0.071 and 0.263; all p < .001). FFIVAT was the index more consistently associated with HRV parameters (ß ranges between -0.507 and 0.529; R2 ranges between 0.235 and 0.275; all p < .001). CONCLUSION: Our study suggests that compound FFIs are better predictors of HRV parameters than either cardiorespiratory fitness or fatness indicators alone. The FFIVAT was the best index in terms of its association to HRV.

Circadian mechanisms in adipose tissue bioenergetics and plasticity.

The circadian clock plays an essential role in coordinating feeding and metabolic rhythms with the light/dark cycle. Disruption of clocks is associated with increased adiposity and metabolic disorders, whereas aligning feeding time with cell-autonomous rhythms in metabolism improves health. Here, we provide a comprehensive overview of recent literature in adipose tissue biology as well as our understanding of molecular mechanisms underlying the circadian regulation of transcription, metabolism, and inflammation in adipose tissue. We highlight recent efforts to uncover the mechanistic links between clocks and adipocyte metabolism, as well as its application to dietary and behavioral interventions to improve health and mitigate obesity.

The Role of Selected Adipocytokines in Ovarian Cancer and Endometrial Cancer.

Due to their multidirectional influence, adipocytokines are currently the subject of numerous intensive studies. Significant impact applies to many processes, both physiological and pathological. Moreover, the role of adipocytokines in carcinogenesis seems particularly interesting and not fully understood. For this reason, ongoing research focuses on the role of these compounds in the network of interactions in the tumor microenvironment. Particular attention should be drawn to cancers that remain challenging for modern gynecological oncology-ovarian and endometrial cancer. This paper presents the role of selected adipocytokines, including leptin, adiponectin, visfatin, resistin, apelin, chemerin, omentin and vaspin in cancer, with a particular focus on ovarian and endometrial cancer, and their potential clinical relevance.

Perivascular Adipose Tissue and Vascular Smooth Muscle Tone: Friends or Foes?

Perivascular adipose tissue (PVAT) is a specialized type of adipose tissue that surrounds most mammalian blood vessels. PVAT is a metabolically active, endocrine organ capable of regulating blood vessel tone, endothelium function, vascular smooth muscle cell growth and proliferation, and contributing critically to cardiovascular disease onset and progression. In the context of vascular tone regulation, under physiological conditions, PVAT exerts a potent anticontractile effect by releasing a plethora of vasoactive substances, including NO, H2S, H2O2, prostacyclin, palmitic acid methyl ester, angiotensin 1-7, adiponectin, leptin, and omentin. However, under certain pathophysiological conditions, PVAT exerts pro-contractile effects by decreasing the production of anticontractile and increasing that of pro-contractile factors, including superoxide anion, angiotensin II, catecholamines, prostaglandins, chemerin, resistin, and visfatin. The present review discusses the regulatory effect of PVAT on vascular tone and the factors involved. In this scenario, dissecting the precise role of PVAT is a prerequisite to the development of PVAT-targeted therapies.

Body fat and muscle in relation to heart rate variability in young-to-middle age men: a cross sectional study.

BACKGROUND: While obesity is recognisably associated with changes in heart rate variability (HRV), the association between skeletal muscle mass and HRV is less clear. AIMS: In this cross sectional study, we analysed the association of body fat (four parameters) and muscle mass (five parameters) with indicators of HRV activity. SUBJECTS AND METHODS: Assessment of body composition and HRV was performed in n = 180 young-to-middle age healthy men exposed to high occupational physical activity, using the multi-frequency bioelectrical impedance device and the PPG-StressFlow® HRV photoplethysmography device, respectively. RESULTS: Mean values of parameters of fat tissue were above normal/reference values. Muscle tissue indicators were higher or within the reference ranges. Fat tissue parameters were significantly higher in participants with lower parasympathetic nervous system (PNS) indicators. Weight-adjusted skeletal muscle index (wSMI) was significantly lower in men with reduced PNS parameters. Fat tissue parameters were negatively correlated with PNS parameters, while wSMI was positively correlated with PNS parameters. CONCLUSIONS: Participants with higher fat mass and lower muscle mass had poorer parasympathetic activity. Since mean values of HRV parameters indicated mild parasympathetic dominance, we conclude that physical activity and consequently good muscle mass potentially compensated for the negative interaction between fat tissue and HRV.

US Army basic combat training alters the relationship between body mass index and per cent body fat.

INTRODUCTION/BACKGROUND: As a proxy for adiposity, body mass index (BMI) provides a practical public health metric to counter obesity-related disease trends. On an individual basis, BMI cannot distinguish fat and lean components of body composition. Further, the relationship between BMI and body composition may be altered in response to physical training. We investigated this dynamic relationship by examining the effect of US Army basic combat training (BCT) on the association between BMI and per cent body fat (%BF). METHODS: BMI and %BF were measured at the beginning (week 1) and end (week 9) of BCT in female (n=504) and male (n=965) trainees. Height and weight were obtained for BMI, and body composition was obtained by dual X-ray absorptiometry. Sensitivity and specificity of BMI-based classification were determined at two BMI thresholds (25 kg/m2 and 27.5 kg/m2). RESULTS: A progressive age-related increase in fat-free mass index (FFMI) was observed, with an inflection point at age 21 years. In soldiers aged 21+, BMI of 25.0 kg/m2 predicted 33% and 29% BF in women and 23% and 20% BF in men and BMI of 27.5 kg/m2 predicted 35% and 31% BF in women and 26% and 22% BF in men, at the start and end of BCT, respectively. Sensitivity and specificity of BMI-based classification of %BF were poor. Soldiers below BMI of 20 kg/m2 had normal instead of markedly reduced %BF, reflecting especially low FFMI. CONCLUSIONS: BCT alters the BMI-%BF relationship, with lower %BF at a given BMI by the end of BCT compared with the beginning, highlighting the unreliability of BMI to try to estimate body composition. The specific BMI threshold of 25.0 kg/m2, defined as 'overweight', is an out-of-date metric for health and performance outcomes. To the extent that %BF reflects physical readiness, these data provide evidence of a fit and capable military force at BMI greater than 25.0 kg/m2.

Research progress of intramuscular fat formation based on co-culture.

Intramuscular fat (IMF) is closely related to the meat quality of livestock and poultry. As a new cell culture technique in vitro, cell co-culture has been gradually applied to the related research of IMF formation because it can simulate the changes of microenvironment in vivo during the process of IMF cell formation. In the co-culture model, in addition to studying the effects of skeletal muscle cells on the proliferation and differentiation of IMF, we can also consider the role of many secretion factors in the formation of IMF, thus making the cell research in vitro closer to the real level in vivo. This paper reviewed the generation and origin of IMF, summarized the existing co-culture methods and systems, and discussed the advantages and disadvantages of each method as well as the challenges faced in the establishment of the system, with emphasis on the current status of research on the formation of IMF for human and animal based on co-culture technology.

Implications of Adipose Tissue Content for Changes in Serum Levels of Exercise-Induced Adipokines: A Quasi-Experimental Study.

Human adipocytes release multiple adipokines into the bloodstream during physical activity. This affects many organs and might contribute to the induction of inflammation. In this study, we aimed to assess changes in circulating adipokine levels induced by intense aerobic and anaerobic exercise in individuals with different adipose tissue content. In the quasi-experimental study, 48 male volunteers (aged 21.78 ± 1.98 years) were assigned to groups depending on their body fat content (BF): LBF, low body fat (<8% BF, n = 16); MBF, moderate body fat (8−14% BF, n = 19); and HBF, high body fat (>14% BF, n = 13). The volunteers performed maximal aerobic effort (MAE) and maximal anaerobic effort (MAnE) exercises. Blood samples were collected at five timepoints: before exercise, immediately after, 2 h, 6 h, and 24 h after each exercise. The selected cytokines were analyzed: adiponectin, follistatin-like 1, interleukin 6, leptin, oncostatin M, and resistin. While the participants' MAnE and MAE performance were similar regardless of BF, the cytokine response of the HBF group was different from that of the others. Six hours after exercise, leptin levels in the HBF group increased by 35%. Further, immediately after MAnE, resistin levels in the HBF group also increased, by approximately 55%. The effect of different BF was not apparent for other cytokines. We conclude that the adipokine exercise response is associated with the amount of adipose tissue and is related to exercise type.

Towards better models for studying human adipocytes in vitro.

With obesity and its comorbidities continuing to rise, we urgently need to improve our understanding of what mechanisms trigger the white adipose tissue to become dysfunctional in response to over-feeding. The recent invent of 3D culturing models has produced several noteworthy protocols for differentiating unilocular adipocytes in vitro, promising to revolutionize the obesity research field by providing more representative adipose tissue models for such mechanistic studies. In parallel, these 3D models provide important insights to how profoundly the microenvironment influences adipocyte differentiation and morphology. This commentary highlights some of the most recent 3D models, including human unilocular vascularized adipocyte spheroids (HUVASs), developed by our lab. We discuss recent developments in the field, provide further insights to the importance of the microvasculature for adipocyte maturation, and summarize what challenges remain to be solved before we can achieve a culture model that fully recapitulates all aspects of human white adipocyte biology in vitro. Taken together, the commentary highlights important recent advances regarding 3D adipocyte culturing and underlines the many advantages these models provide over traditional 2D cultures, with the aim of convincing more laboratories to switch to 3D models.