Dispersal of Abdominal Visceral; Subcutaneous, Visceral to Subcutaneous Adiposity Ratio and Metabolic Syndrome in A Sample of Obese Egyptians

Background: Visceral to subcutaneous adiposity ratio (VSR) may be more crucial than visceral and subcutaneous adipose tissue per se. It reflects relative distribution of abdominal adiposity which is a better indicator of cardio-meta­bolic risk. Aim: to examine if the VSR has diagnostic value in identifying metabolic syndrome (MS) compared with VAT and SAT among sample of obese Egyptians. Subjects and Methods: The over here study included 456 obese Egyptian adults (106 male and 350 female), ageing across 25- 55 years. All participants subjected to blood pressure and anthropometric assessment, abdominal ultrasound, and laboratory tests. Results: Males had quite high level of triglycerides and low HDL than females, who had significantly higher frequency of wide WC than men. There was insignificant sex difference in the frequency of MS. VAT and SAT were significantly higher in presence of wide WC and hypertension among both sexes. Also, VSR was significantly higher in presence of wide WC and hypertension among women only. While presence of MS led to significantly higher value of SAT among men, and VAT among women. Area under the curves (AUCs) for VAT, SAT and VSR; to predict MS; were 0.59, 0.63 and 0.46 among men and 0.63, 0.56 and 0.55 among women. Conclusion: Visceral and subcutaneous adipose tissue; not visceral/subcutaneous ratio; were significantly affected by the presence of MS in both sexes. SAT was significantly superior among men, while VAT was superior among women. VSR cannot be used as a predictor of MS.

Prognostic Role of Subcutaneous and Visceral Adiposity in Hospitalized Octogenarians with COVID-19

Background: We investigated the prognostic significance of visceral and subcutaneous adiposity in octogenarians with COVID-19. Methods: This paper presents a monocentric retrospective study that was conducted in acute geriatric wards with 64 hospitalized patients aged 80+ who had a diagnosis of COVID-19 and who underwent a chest CT scan. A quantification of the subcutaneous, visceral, and total fat areas was performed after segmentations on the first abdominal slice caudal to the deepest pleural recess on a soft-tissue window setting. Logistic regression models were applied to investigate the association with in-hospital mortality and the extent of COVID-19 pneumonia. Results: The patients had a mean age of 86.4 ± 6.0 years, and 46.9% were male, with a mean BMI of 24.1 ± 4.4Kg/m2 and mortality rate of 32.8%. A higher subcutaneous fat area had a protective effect against mortality (OR 0.416; 0.183–0.944 95% CI; p = 0.036), which remained significant after adjustments for age, sex, and BMI (OR 0.231; 0.071–0.751 95% CI; p = 0.015). Inversely, higher abdominal circumference, total fat area, subcutaneous fat area, and visceral fat were associated with worse COVID-19 pneumonia, with the latter presenting the strongest association after adjustments for age, sex, and BMI (OR 2.862; 1.523–5.379 95% CI; p = 0.001). Conclusion: Subcutaneous and visceral fat areas measured on chest CT scans were associated with prognosis in octogenarians with COVID-19.

Development of Visceral and Subcutaneous-Abdominal Adipose Tissue in Breastfed Infants during First Year of Lactation

This study aimed to investigate relationships between infant abdominal visceral and subcutaneous adiposity and human milk (HM) components and maternal body composition (BC) during first year of lactation. Subcutaneous-abdominal depth (SAD), subcutaneous-abdominal fat area (SFA), visceral depth (VD) and preperitoneal fat area of 20 breastfed infants were assessed at 2, 5, 9 and 12 months using ultrasound. Maternal BC was determined with bioimpedance spectroscopy. HM macronutrients and bioactive components concentrations and infant 24-h milk intake were measured and calculated daily intakes (CDI) determined. Maternal adiposity associated with infant SFA (negatively at 2, 5, 12, positively at 9 months, all overall p < 0.05). 24-h milk intake positively associated with infant SAD (p = 0.007) and VD (p = 0.013). CDI of total protein (p = 0.013), total carbohydrates (p = 0.004) and lactose (p = 0.013) positively associated with SFA. Lactoferrin concentration associated with infant VD (negatively at 2, 12, positively at 5, 9 months, overall p = 0.003). CDI of HM components and maternal adiposity have differential effects on development of infant visceral and subcutaneous abdominal adiposity. Maintaining healthy maternal BC and continuing breastfeeding to 12 months and beyond may facilitate favourable BC development reducing risk of obesity.

88The Role of Visceral Adiposity in the Metabolic Phenotype of multi-ethnic South-East Asian population

Background Ethnic Asians are known to exhibit worse metabolic phenotypes as compared to Caucasians despite lower body mass index1, 2. Ethnic South-Asians and Malays were also found to display greater insulin resistance than Chinese3. One potential biological mechanism for this phenomenon is the inter-ethnic differences in the visceral adiposity deposition4. Here we hypothesised that visceral adiposity contributes to ethnic differences in metabolic phenotype more than subcutaneous adiposity. Methods We quantified total, subcutaneous and visceral adipose deposition (BMI, waist circumferences, Dual-energy X-ray absorptiometry [DEXA]) and metabolic phenotypes (blood pressure, fasting glucose and lipid profile, HbA1c) in 3403 participants. Analyses were adjusted for age, and sex. Results Participants were 40.6% male, mean age 49.7±11.4 years, Chinese: Malays: South-Asians in 72:9:19 ratio. Ethnic Malays and South-Asians had raised blood pressure, fasting glucose, triglycerides, HbA1c, reduced HDL, and higher total and visceral fat than Chinese (P &lt; 0.001), independent of covariates. Increased adiposity was strongly associated with poorer metabolic phenotype (all P &lt; 0.0001), with strongest associations found amongst visceral Fat Mass Index (□□95%CI]=0.48[0.20;0.23]) and android/gynoid ratio (□[95%CI]=0.55[1.31;1.63]) with triglycerides levels. Visceral adiposity contributed 17-40% (all P &lt; 0.0001) to the variance in the associations of ethnic Malays and South-Asians with metabolic phenotypes, 3-7% higher than subcutaneous adiposity. Conclusions Visceral adiposity contributes to poorer metabolic phenotype in ethnic Malays and South Asians as compared to Chinese. Key messages Visceral adiposity expansion is an important determinant of metabolic health in Asian populations.

Beige adipocytes mediate the neuroprotective and anti-inflammatory effects of subcutaneous fat in obese mice

Visceral obesity increases risk of cognitive decline in humans, but subcutaneous adiposity does not. Here, we report that beige adipocytes are indispensable for the neuroprotective and anti-inflammatory effects of subcutaneous fat. Mice lacking functional beige fat exhibit accelerated cognitive dysfunction and microglial activation with dietary obesity. Subcutaneous fat transplantation also protects against chronic obesity in wildtype mice via beige fat-dependent mechanisms. Beige adipocytes restore hippocampal synaptic plasticity following transplantation, and these effects require the anti-inflammatory cytokine interleukin-4 (IL4). After observing beige fat-mediated induction of IL4 in meningeal T-cells, we investigated the contributions of peripheral lymphocytes in donor fat. There was no sign of donor-derived lymphocyte trafficking between fat and brain, but recipient-derived lymphocytes were required for the effects of transplantation on cognition and microglial morphology. These findings indicate that beige adipocytes oppose obesity-induced cognitive impairment, with a potential role for IL4 in the relationship between beige fat and brain function.

Hyperinsulinemic Compensation For Insulin Resistance Occurs Independent Of Elevated Glycemia In Male Dogs

Insulin resistance (IR) engenders a compensatory increase in plasma insulin. Inadequate compensation is a primary element in the pathogenesis of Type 2 diabetes. The signal which heralds developing IR and initiates hyperinsulinemic compensation is not known. It has often been assumed to be increased glucose. We tested this assumption by determining whether development of fasting and/or glucose-stimulated hyperinsulinemia with diet-induced insulin resistance occurs because of concomitant elevation of glycemia. Male dogs (n=58) were fed a hypercaloric, fat-supplemented diet for 6 wks. Dogs underwent MRI to quantify total and regional (visceral, subcutaneous) adiposity as well as euglycemic hyperinsulinemic clamps. A subset of animals also underwent an insulin-modified intravenous glucose tolerance test (IVGTT) to assess insulin sensitivity, acute insulin response (AIRg), and glucose effectiveness. Fat feeding caused modest weight gain, increased visceral and subcutaneous fat, and IR at both peripheral and hepatic levels. Hyperinsulinemic compensation was observed in fasting levels as well as increased AIRg. However, we observed absolutely no increase in carefully measured fasting, evening (6-8 pm) or nocturnal glycemia (2-4 am). IR and hyperinsulinemia occurred despite no elevation in 24-hour glucose. Compensatory development of hyperinsulinemia during diet-induced insulin resistance occurs without elevated fasting or 24-hour glycemia. These data refute the idea that glucose itself is a requisite signal for β-cell upregulation. Alternative feedback mechanisms need to be identified.

Almond Consumption Decreases Android Fat Mass Percentage in Adults With High Android Subcutaneous Adiposity but Does Not Change HbA1c

Objectives The purpose of this study was to determine if the mixed evidence of almond consumption on HbA1c stems from testing people with different body fat distributions (BFD) associated with different risks of glucose intolerance. Methods A 6-month RCT in 134 adults was conducted. Participants were randomly assigned to the almond or control treatment based on their BFD. Those in the almond group consumed 0.75 oz of almonds with their breakfast and as their afternoon snack (1.5 oz almonds/day) every day, and were instructed not to consume any other nuts. Those in the control treatment continued their habitual breakfast and afternoon snack routines, but were instructed not to consume any nuts. At 0 and 6 months, body composition was measured and blood samples were collected for analyses of HbA1c, glycemia and lipemia. Appetite and dietary intake data were recorded at 0, 2, 4, and 6 months and a blood sample was obtained for compliance testing. Body weight was measured every two weeks. An intention-to-treat linear mixed model analysis was performed with Bonferroni pairwise comparisons on diet quality, energy intake, HbA1c, and body composition change values. Results Incorporating almonds into the diet increased total diet quality by 8.3 ± 2.1% over the intervention (P = 0.001). Participants consuming almonds ingested 195 ± 87 kcals/day more than participants in the control group (P = 0.027), but this did not result in differences in body weight (P &gt; 0.3). The almond, high android subcutaneous adiposity (SAT) group had a greater reduction in android fat mass % (P = 0.038), preserved android lean mass % (P = 0.042), and tended to decrease android VAT mass (P = 0.079) compared to those in the control, high SAT group. There were no differences of HbA1c between groups (P &gt; 0.05). Conclusions Incorporating 1.5-oz of almonds into the diet improves diet quality without promoting positive energy balance and weight gain. Long-term consumption of almonds may also improve android composition in those with high android SAT. However, testing people with different BFD does not account for the mixed evidence on almond consumption and HbA1c. Funding Sources This study was funded by the Almond Board of California.

Hepatic Igf1-deficiency protects against atherosclerosis in female mice

Atherosclerosis is the leading cause of cardiovascular disease (CVD) with distinct sex-specific pathogenic mechanisms that are poorly understood. Aging, a major independent risk factor of atherosclerosis, correlates with a decline in circulating insulin-like growth factor-1 (IGF-1). However, the precise effects of Igf1 on atherosclerosis remain unclear. In the present study, we assessed the essential role of hepatic Igf1, the major source of circulating IGF-1, in atherogenesis. We generated hepatic Igf1-deficient atherosclerosis-prone ApoE null mice (L-Igf1 -/-ApoE -/-) using the Cre-loxP system driven by the Albumin promoter. Starting at 6 weeks of age, these mice along with littermate controls, separated into male and female groups, were placed on an atherogenic diet for 18-19 weeks. We show that hepatic Igf1-deficiency led to atheroprotection with reduced plaque macrophages in females, without significant effects in males. This protection in atherosclerosis in females was associated with increased subcutaneous adiposity with impaired lipolysis. Moreover, this impaired lipid homeostasis was associated with disrupted adipokine secretion with reduced circulating IL-6 levels. Together, our data show that endogenous hepatic Igf1 plays a sex-specific regulatory role in atherogenesis potentially through athero-promoting effects of adipose tissue-derived IL-6 secretion. These data provide potential novel sex-specific mechanisms in the pathogenesis of atherosclerosis.

Adiposity and response to androgen signaling inhibition (ASI) in men with metastatic castration-resistant prostate cancer (mCRPC).

72 Background: Improved understanding of how host factors influence the efficacy and toxicity of ASI could improve outcomes. Adiposity increases the risk for recurrence and lethal disease in men with localized prostate cancer. Few studies have evaluated the influence of adiposity in metastatic prostate cancer, and in these studies, adiposity was associated with improved outcomes, a potential “obesity paradox”. Herein, we assess whether adiposity is associated with response to maximal ASI in mCRPC and assess how individual body composition measurements interact to influence outcomes. Methods: Men with mCRPC uniformly treated on a prospective clinical trial with abiraterone acetate plus apalutamide were included in this post-hoc analysis (NCT02703623). Responders were defined as those with a decrease in PSA of > 50% after 8 weeks of therapy. Body composition was assessed at the level of L3 on baseline CT scan at trial registration using Slice-O-Matic version 5.0. Body composition indices were normalized for height (m2). Non-parametric Kruskal-Wallis test was used to evaluate associations between continuous baseline measures. A multivariable CART model was used to determine if baseline measures could divide patients into distinct risk groups. Results: In 186 men with mCRPC, responders to maximal ASI (n = 128) had higher subcutaneous adiposity (SATi, 79.3 vs. 67.6, p = 0.02), visceral adiposity (VATi, 76.4 vs. 61.5, p = 0.03), and body mass index (BMI, 30.3 vs. 29.2, p = 0.04). There was a strong correlation between BMI and SAT (r = 0.81). In exploratory multivariable modeling, BMI and VATi had the strongest associations with response to ASI. Specifically, men with a BMI ≥ 26.73 had a higher response rate (75% vs. 46%). For men with a BMI < 26.73, a VATi ≥ 24.7 enriched for response to therapy (86% vs. 26%). Conclusions: Elevated subcutaneous and visceral adiposity is associated with improved response to maximal ASI in men with mCRPC. In hypothesis-generating models, visceral adiposity had the strongest association with response to ASI in men with lower BMI. Further studies need to assess how and when adiposity becomes favorable for outcomes in advanced prostate cancer.