Adipose Tissue Inflammation.

In recent decades, obesity has become one of the most common metabolic diseases [...].

Effects of estradiol on fat in men undergoing androgen deprivation therapy: a randomized trial.

OBJECTIVE: Indirect evidence suggests that the effects of testosterone on fat mass in men are dependent on aromatization to estradiol (E2). However, no controlled study has assessed the effects of E2 in the absence of testosterone. DESIGN: Six-month randomized, placebo-controlled trial with the hypothesis that men randomized to E2 would reduce their fat mass. METHODS: Seventy-eight participants receiving androgen deprivation therapy for prostate cancer were randomized to 0.9 mg of 0.1% E2 gel per day, or matched placebo. Dual x-ray absorptiometry body composition was measured at baseline, month 3, and month 6. The primary outcome was total fat mass. RESULTS: Serum E2 increased in the estradiol group over 6 months compared to placebo, and mean-adjusted difference (MAD) was 207 pmol/L (95% CI: 123-292), P < 0.001. E2 treatment changed total fat mass, MAD 1007 g (95% CI: 124-1891), but not significantly, so P = 0.09. There were other consistent non-significant trends toward increased proportional fat mass, MAD 0.8% (95% CI: 0.0-1.6), P= 0.15; gynoid fat, MAD 147 g (95% CI: 2-293), P = 0.08; visceral fat, 53 g (95% CI: 1-105) P = 0.13; and subcutaneous fat, MAD 65 g (95% CI: 5-125), P = 0.11. Android fat increased, MAD 164 g (95% CI: 41-286), P = 0.04. CONCLUSION: Contrary to our hypothesis, we provide suggestive evidence that E2 acting in the absence of testosterone, may increase total and regional fat mass in men. Given the premature closure of clinical trials due to the COVID pandemic, this potentially important observation should encourage additional studies to confirm or refute whether E2 promotes fat expansion in the absence of testosterone.

Obesity and immune status in children.

PURPOSE OF REVIEW: Childhood obesity, with persistent chronic inflammation, is a worldwide epidemic. Obesity causes dysregulation throughout the immune system, affecting the balance and levels of cytokines, adipokines, and innate and adaptive immune cells. The present review focuses on the impact of obesity on immune function in children: altering the baseline activation state of immune cells and affecting the ability of the host to combat pathogens and malignancy and respond appropriately to vaccination. RECENT FINDINGS: Obesity causes dysregulation of the immune system. Single-cell RNA-sequencing of adipose tissue and resident immune cells is quantifying the impact of obesity on the frequency of immune cell subsets and their states. The system-wide alterations in immune function in obesity are most evident upon perturbation, including the response to infection (e.g. increased risk of severe COVID-19 in the ongoing pandemic), vaccination, and malignancy. However, mechanistic research in pediatric obesity is limited and this impacts our ability to care for these children. SUMMARY: We must better understand baseline and perturbed immune health in obese children to determine how to account for altered frequency and function of humoral and cellular immune components in acute infection, during vaccine design and when considering therapeutic options for this complex, medically vulnerable group.

Oxidative Stress Linking Obesity and Cancer: Is Obesity a 'Radical Trigger' to Cancer?

Obesity is on the rise worldwide, and consequently, obesity-related non-communicable diseases are as well. Nutritional overload induces metabolic adaptations in an attempt to restore the disturbed balance, and the byproducts of the mechanisms at hand include an increased generation of reactive species. Obesity-related oxidative stress causes damage to vulnerable systems and ultimately contributes to neoplastic transformation. Dysfunctional obese adipose tissue releases cytokines and induces changes in the cell microenvironment, promoting cell survival and progression of the transformed cancer cells. Other than the increased risk of cancer development, obese cancer patients experience higher mortality rates and reduced therapy efficiency as well. The fact that obesity is considered the second leading preventable cause of cancer prioritizes the research on the mechanisms connecting obesity to cancerogenesis and finding the solutions to break the link. Oxidative stress is integral at different stages of cancer development and advancement in obese patients. Hypocaloric, balanced nutrition, and structured physical activity are some tools for relieving this burden. However, the sensitivity of simultaneously treating cancer and obesity poses a challenge. Further research on the obesity-cancer liaison would offer new perspectives on prevention programs and treatment development.

Computed tomography and nuclear medicine for the assessment of coronary inflammation: clinical applications and perspectives.

There is increasing evidence that in patients with atherosclerotic cardiovascular disease (ASCVD) under optimal medical therapy, a persisting dysregulation of the lipid and glucose metabolism, associated with adipose tissue dysfunction and inflammation, predicts a substantial residual risk of disease progression and cardiovascular events. Despite the inflammatory nature of ASCVD, circulating biomarkers such as high-sensitivity C-reactive protein and interleukins may lack specificity for vascular inflammation. As known, dysfunctional epicardial adipose tissue (EAT) and pericoronary adipose tissue (PCAT) produce pro-inflammatory mediators and promote cellular tissue infiltration triggering further pro-inflammatory mechanisms. The consequent tissue modifications determine the attenuation of PCAT as assessed and measured by coronary computed tomography angiography (CCTA). Recently, relevant studies have demonstrated a correlation between EAT and PCAT and obstructive coronary artery disease, inflammatory plaque status and coronary flow reserve (CFR). In parallel, CFR is well recognized as a marker of coronary vasomotor function that incorporates the haemodynamic effects of epicardial, diffuse and small-vessel disease on myocardial tissue perfusion. An inverse relationship between EAT volume and coronary vascular function and the association of PCAT attenuation and impaired CFR have already been reported. Moreover, many studies demonstrated that 18F-FDG PET is able to detect PCAT inflammation in patients with coronary atherosclerosis. Importantly, the perivascular FAI (fat attenuation index) showed incremental value for the prediction of adverse clinical events beyond traditional risk factors and CCTA indices by providing a quantitative measure of coronary inflammation. As an indicator of increased cardiac mortality, it could guide early targeted primary prevention in a wide spectrum of patients. In this review, we summarize the current evidence regarding the clinical applications and perspectives of EAT and PCAT assessment performed by CCTA and the prognostic information derived by nuclear medicine.

Body Fat Reduction Effect of Bifidobacterium breve B-3: A Randomized, Double-Blind, Placebo Comparative Clinical Trial.

This double-blind, randomized clinical trial aimed to evaluate the efficacy and safety of Bifidobacterium breve B-3 (BB-3) for reducing body fat. Healthy individuals were randomized into the BB-3 or placebo group (1:1). Dual-energy X-ray absorptiometry was used to evaluate body fat reduction objectively. In the BB-3 group, body weight was lower than before BB-3 ingestion. Regarding waist circumference, hip circumference, and waist/hip circumference ratio, waist circumference and hip circumference were lower in the BB-3 group than in the placebo group at 12 weeks; the waist/hip circumference ratio was found to decrease at each visit in the BB-3 group, although there was no significant difference in the amount of change after 12 weeks. BB-3 did not cause any severe adverse reactions. Body fat was significantly lower in the BB-3 group than in the placebo group. In conclusion, ingesting BB-3 significantly reduces body weight, waist circumference, and hip circumference. Thus, BB-3 is safe and effective for reducing body fat.

Prevalence and clinical implications of abnormal body composition phenotypes in patients with COVID-19: a systematic review.

BACKGROUND: The impact of body composition (BC) abnormalities on COVID-19 outcomes remains to be determined. OBJECTIVES: We summarized the evidence on BC abnormalities and their relationship with adverse clinical outcomes in patients with COVID-19. METHODS: A systematic search was conducted up until 26 September, 2022 for observational studies using BC techniques to quantify skeletal muscle mass (or related compartments), muscle radiodensity or echo intensity, adipose tissue (AT; or related compartments), and phase angle (PhA) in adults with COVID-19. Methodological quality of studies was assessed using the Newcastle-Ottawa Scale. A synthesis without meta-analysis was conducted to summarize the prevalence of BC abnormalities and their significant associations with clinical outcomes. RESULTS: We included 62 studies (69.4% low risk of bias) with 12-1138 participants, except 3 studies with ≤490,301 participants. Using CT and different cutoff values, prevalence ranged approximately from 22% to 90% for low muscle mass, 12% to 85% for low muscle radiodensity, and 16% to 70% for high visceral AT. Using BIA, prevalence of high FM was 51%, and low PhA was 22% to 88%. Mortality was inversely related to PhA (3/4 studies) and positively related to intra- and intermuscular AT (4/5 studies), muscle echo intensity (2/2 studies), and BIA-estimated FM (2/2 studies). Intensive care unit (ICU) admission was positively related to visceral AT (6/7 studies) and total AT (2/3 studies). Disease severity and hospitalization outcomes were positively related to intra- and intermuscular AT (2/2 studies). Inconsistent associations were found for the rest of the BC measures and hospitalization outcomes. CONCLUSIONS: Abnormalities in BC were prevalent in patients with COVID-19. Although conflicting associations were observed among certain BC abnormalities and clinical outcomes, higher muscle echo intensity (reflective of myosteatosis) and lower PhA were more consistently associated with greater mortality risk. Likewise, high intra- and intermuscular AT and visceral AT were associated with mortality and ICU admission, respectively. This trial was registered at PROSPERO as CRD42021283031.

Elevated FAI Index of Pericoronary Inflammation on Coronary CT Identifies Increased Risk of Coronary Plaque Vulnerability after COVID-19 Infection.

Inflammation is a key factor in the development of atherosclerosis, a disease characterized by the buildup of plaque in the arteries. COVID-19 infection is known to cause systemic inflammation, but its impact on local plaque vulnerability is unclear. Our study aimed to investigate the impact of COVID-19 infection on coronary artery disease (CAD) in patients who underwent computed tomography angiography (CCTA) for chest pain in the early stages after infection, using an AI-powered solution called CaRi-Heart®. The study included 158 patients (mean age was 61.63 ± 10.14 years) with angina and low to intermediate clinical likelihood of CAD, with 75 having a previous COVID-19 infection and 83 without infection. The results showed that patients who had a previous COVID-19 infection had higher levels of pericoronary inflammation than those who did not have a COVID-19 infection, suggesting that COVID-19 may increase the risk of coronary plaque destabilization. This study highlights the potential long-term impact of COVID-19 on cardiovascular health, and the importance of monitoring and managing cardiovascular risk factors in patients recovering from COVID-19 infection. The AI-powered CaRi-Heart® technology may offer a non-invasive way to detect coronary artery inflammation and plaque instability in patients with COVID-19.

Perigenual anterior cingulate cortex and its structural covariance as predictors for future body fat gain in young adults.

OBJECTIVE: This study aimed to examine whether baseline gray matter (GM) volume and structural covariance patterns could predict body fat gain over 1 to 2 years in a relatively large sample. METHODS: Voxel-based morphometry (VBM) analysis was applied to examine the association between baseline GM volume and body fat gain in 502 participants over 1 to 2 years. Furthermore, this study tested whether the structural covariances between the regions identified as seeds from VBM analysis and the rest of the brain were associated with future body fat gain. RESULTS: A significant positive association was observed between baseline GM volume in the perigenual anterior cingulate cortex (pgACC) and body fat gain over 1 to 2 years. Furthermore, relative to those with lower future body fat gain, pgACC covaried more extensively with the middle frontal gyrus, middle temporal gyrus, inferior temporal gyrus, and cerebellum in participants with higher future body fat gain. CONCLUSIONS: Using VBM and structural covariance network analysis, the current study revealed that higher GM volume of pgACC and its increased structural covariances with specific brain regions were associated with future weight gain, which may guide the development of more effective prevention and treatment interventions for obesity.

Comment on Sung et al. Body Fat Reduction Effect of Bifidobacterium breve B-3: A Randomized, Double-Blind, Placebo Comparative Clinical Trial. Nutrients 2023, 15, 28.

I read with interest the paper by Sung et al. entitled "Body Fat Reduction Effect of Bifidobacterium breve B-3: A Randomized, Double-Blind, Placebo Comparative Clinical Trial" where a reduction in body fat mass after Bifidobacterium breve B-3 (BB-3) ingestion for 12 weeks was reported [...].

In vitro studies of the renin-angiotensin system in human adipose tissue/adipocytes and possible relationship to SARS-CoV-2: a scoping review.

The renin-angiotensin system (RAS) operates within adipose tissue. Obesity-related changes can affect adipose RAS, predisposing to hypertension, type 2 diabetes, and possibly severe COVID-19. We evaluated the in vitro research on human adipose RAS and identified gaps in the literature. Medline (Ovid), Embase (Ovid), Web of Science, Scopus, and 1findr were searched to identify relevant studies. Fifty primary studies met our inclusion criteria for analysis. Expression of RAS components (n = 14), role in differentiation (n = 14), association with inflammation (n = 15) or blood pressure (n = 7) were investigated. We found (1) obesity-related changes in RAS were frequently studied (30%); (2) an upswing of articles investigating adipose ACE-2 expression since the COVID-19 pandemic; (3) a paucity of papers on AT2R and Ang (1-7)/MasR which counterbalance Ang II/ART1; (4) weight loss lowered adipose ACE-2 mRNA expression; and (5) angiotensin receptor blockers (ARBs) reduced deleterious effects of angiotensin II. Overall, these studies link Ang II/ATR1 signalling to impaired adipogenesis and a pro-inflammatory dysfunctional adipose tissue, with ATR1 blockade limiting these responses. ACE-2 may mitigate Ang II effects by converting it to Ang(1-7) which binds MasR. More work is needed to understand adipose RAS in various pathologic states such as obesity and COVID-19 infection.T.

Lipolysis is accompanied by immune microenvironment remodeling in adipose tissue of obesity with different exercise intensity.

OBJECTIVE: Obesity and overweight are risk factors for chronic disease worldwide. The purpose of this study was to compare the transcriptome of exercise-induced fat mobilization in obese people, and to explore the effect of different exercise intensity on the correlation of immune microenvironment remodeling and lipolysis in adipose tissue. MATERIALS AND METHODS: Microarray datasets of adipose tissue before and after exercise were downloaded from the Gene Expression Omnibus. Then, we used gene-enrichment analysis and PPI-network construction to elucidate the function and enrichment pathways of the differentially expressed genes (DEGs) and to identify the central genes. A network of protein-protein interactions was obtained using STRING and visualized with Cytoscape. RESULTS: A total of 929 DEGs were identified between 40 pre-exercise (BX) samples and 65 post-exercise (AX) samples from GSE58559, GSE116801, and GSE43471. Among these DEGs, adipose tissue-expressed genes were duly recognized. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicated that DEGs were mostly enriched in lipid metabolism. Studies have found that mitogen-activated protein kinase (MAPK) signaling pathway and forkhead box O (FOXO) signaling pathway are up-regulated, while Ribosome, coronavirus disease (COVID-19) and IGF-1 gene are down-regulated. Although we found the up-regulated genes that noted IL-1 among others, and the down-regulated gene was IL-34. The increase of inflammatory factors leads to changes in cellular immune microenvironment, and high-intensity exercise leads to increased expression of inflammatory factors in adipose tissue, leading to inflammatory responses. CONCLUSIONS: Exercise at different intensities leads to the degradation of adipose and is accompanied by changes in the immune microenvironment within adipose tissue. High intensity exercise can cause the imbalance of immune microenvironment of adipose tissue while causing fat degradation. Therefore, moderate intensity and below exercise is the best way for the general population to reduce fat and weight.

Beyond energy balance regulation: The underestimated role of adipose tissues in host defense against pathogens.

Although the adipose tissue (AT) is a central metabolic organ in the regulation of whole-body energy homeostasis, it is also an important endocrine and immunological organ. As an endocrine organ, AT secretes a variety of bioactive peptides known as adipokines - some of which have inflammatory and immunoregulatory properties. As an immunological organ, AT contains a broad spectrum of innate and adaptive immune cells that have mostly been studied in the context of obesity. However, overwhelming evidence supports the notion that AT is a genuine immunological effector site, which contains all cell subsets required to induce and generate specific and effective immune responses against pathogens. Indeed, AT was reported to be an immune reservoir in the host's response to infection, and a site of parasitic, bacterial and viral infections. In addition, besides AT's immune cells, preadipocytes and adipocytes were shown to express innate immune receptors, and adipocytes were reported as antigen-presenting cells to regulate T-cell-mediated adaptive immunity. Here we review the current knowledge on the role of AT and AT's immune system in host defense against pathogens. First, we will summarize the main characteristics of AT: type, distribution, function, and extraordinary plasticity. Second, we will describe the intimate contact AT has with lymph nodes and vessels, and AT immune cell composition. Finally, we will present a comprehensive and up-to-date overview of the current research on the contribution of AT to host defense against pathogens, including the respiratory viruses influenza and SARS-CoV-2.

Obesity and COVID-19: Mechanistic Insights From Adipose Tissue.

Obesity is associated with an increase in morbidity and mortality from coronavirus disease 2019 (COVID-19). The risk is related to the cytokine storm, a major contributor to multiorgan failure and a pathological character of COVID-19 patients with obesity. While the exact cause of the cytokine storm remains elusive, disorders in energy metabolism has provided insights into the mechanism. Emerging data suggest that adipose tissue in obesity contributes to the disorders in several ways. First, adipose tissue restricts the pulmonary function by generation of mechanical pressures to promote systemic hypoxia. Second, adipose tissue supplies a base for severe acute respiratory syndrome coronavirus 2 entry by overexpression of viral receptors [angiotensin-converting enzyme 2 and dipeptidyl peptidase 4]. Third, impaired antiviral responses of adipocytes and immune cells result in dysfunction of immunologic surveillance as well as the viral clearance systems. Fourth, chronic inflammation in obesity contributes to the cytokine storm by secreting more proinflammatory cytokines. Fifth, abnormal levels of adipokines increase the risk of a hyperimmune response to the virus in the lungs and other organs to enhance the cytokine storm. Mitochondrial dysfunction in adipocytes, immune cells, and other cell types (endothelial cells and platelets, etc) is a common cellular mechanism for the development of cytokine storm, which leads to the progression of mild COVID-19 to severe cases with multiorgan failure and high mortality. Correction of energy surplus through various approaches is recommended in the prevention and treatment of COVID-19 in the obese patients.

COVID-19: Understanding the impact of anti-hypertensive drugs and hydroxychloroquine on the ACE1 and ACE2 in lung and adipose tissue in SHR and WKY rats.

Hypertensive individuals taking anti-hypertensive drugs from renin-angiotensin system inhibitors may exhibit a more severe evolution of the disease when contracting the SARS-CoV-2 virus (COVID-19 disease) due to potential increases in ACE2 expression. The study investigated ACE1 and ACE2 axes and hydroxychloroquine in the lungs and adipose tissue of male and female normotensive Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHRs). SHRs were treated with losartan (10 mg/kg/day) or captopril (10 mg/kg/day) for 14 days or 7 days with hydroxychloroquine (200 mg/kg/day) in drinking water. WKY rats were also treated for 7 days with hydroxychloroquine. Blood pressure (BP), protein, and mRNA expression of ACE1 and ACE2 were analyzed in serum, adipose, and lung tissues. Losartan and captopril reduced BP in both sexes in SHR, whereas hydroxychloroquine increased BP in WKY rats. Losartan reduced ACE2 in serum and lungs in both sexes and in adipose tissue of male SHRs. Captopril decreased ACE2 protein in the lung of females and in adipose tissue in both sexes of SHRs. Hydroxychloroquine decreased ACE1 and ACE2 proteins in the lungs in both sexes and adipose tissue in male SHRs. In female WKY rats, ACE2 protein was lower only in the lungs and adipose tissue. Losartan effectively inhibited ACE2 in male and captopril in female SHRs. Hydroxychloroquine inhibited ACE2 in male SHRs and female WKY rats. These results further our understanding of the ACE2 mechanism in patients under renin-angiotensin anti-hypertensive therapy and in many trials using hydroxychloroquine for COVID-19 treatment and potential sex differences in response to drug treatment.

Immune Cell Activation in Obesity and Cardiovascular Disease.

PURPOSE OF REVIEW: In this review, we focus on immune cell activation in obesity and cardiovascular disease, highlighting specific immune cell microenvironments present in individuals with atherosclerosis, non-ischemic heart disease, hypertension, and infectious diseases. RECENT FINDINGS: Obesity and cardiovascular disease are intimately linked and often characterized by inflammation and a cluster of metabolic complications. Compelling evidence from single-cell analysis suggests that obese adipose tissue is inflammatory and infiltrated by almost all immune cell populations. How this inflammatory tissue state contributes to more systemic conditions such as cardiovascular and infectious disease is less well understood. However, current research suggests that changes in the adipose tissue immune environment impact an individual's ability to combat illnesses such as influenza and SARS-CoV2. Obesity is becoming increasingly prevalent globally and is often associated with type 2 diabetes and heart disease. An increased inflammatory state is a major contributor to this association. Widespread chronic inflammation in these disease states is accompanied by an increase in both innate and adaptive immune cell activation. Acutely, these immune cell changes are beneficial as they sustain homeostasis as inflammation increases. However, persistent inflammation subsequently damages tissues and organs throughout the body. Future studies aimed at understanding the unique immune cell populations in each tissue compartment impacted by obesity may hold potential for therapeutic applications.

Susceptibility of Fat Tissue to SARS-CoV-2 Infection in Female hACE2 Mouse Model.

The coronavirus disease (COVID-19) is a highly contagious viral illness caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). COVID-19 has had a catastrophic effect globally causing millions of deaths worldwide and causing long-lasting health complications in COVID-19 survivors. Recent studies including ours have highlighted that adipose tissue can act as a reservoir where SARS-CoV-2 can persist and cause long-term health problems. Here, we evaluated the effect of SARS-CoV-2 infection on adipose tissue physiology and the pathogenesis of fat loss in a murine COVID-19 model using humanized angiotensin-converting enzyme 2 (hACE2) mice. Since epidemiological studies reported a higher mortality rate of COVID-19 in males than in females, we examined hACE2 mice of both sexes and performed a comparative analysis. Our study revealed for the first time that: (a) viral loads in adipose tissue and the lungs differ between males and females in hACE2 mice; (b) an inverse relationship exists between the viral loads in the lungs and adipose tissue, and it differs between males and females; and (c) CoV-2 infection alters immune signaling and cell death signaling differently in SARS-CoV-2 infected male and female mice. Overall, our data suggest that adipose tissue and loss of fat cells could play important roles in determining susceptibility to CoV-2 infection in a sex-dependent manner.