Cross-sectional association study of hedonic hunger, self-control, cognitive distortion, and well-being with adiposity measures among a sample of urban Malaysian adults.

BACKGROUND: We assessed the association of hedonic hunger, self-control (impulsivity and restraint), cognitive distortion (CD), and well-being with adiposity measures such as waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), body mass index (BMI), total body fat (TBF), subcutaneous fat (SF), visceral fat level (VFL), skeletal muscle percentage (SM), and resting metabolism (RM), among a sample of urban Malaysian adults at Sunway University and Sunway College, Selangor, Malaysia. METHODS: Among 186 participants (M/F = 51/135; aged 22.1 ± 5.0), psychometrics were assessed using Power of Food Scale (PFS), Brief Self-Control Scale, CD Questionnaire (CD-Quest), and WHO-5 Well-being Index. Blood pressures, anthropometrics and body compositions were also measured using standard methods and bioimpedance. RESULTS: Men had significantly higher well-being, but lower overall self-control, impulsivity and Food Available hedonic hunger. Those with moderate/severe CD had higher odds ratio (OR) of having high central adiposity, compared with those with absent/slight CD (OR: 2.52;95% CI: 1.14, 5.61; p = 0.023 for WC and OR: 2.50; 95% CI: 1.19, 5.23; p = 0.015 for WHR). Higher CD and PFS scores were strongly significantly correlated with higher systolic blood pressure (SBP), WC, WHR, WHtR, BMI, TBF, SF, VFL and RM. Lower self-control was weakly correlated with higher WC, while lower impulsivity and restraint were weakly correlated with higher VFL. Those who were overweight, obese, and in high TBF class had significantly higher PFS Aggregate Factor scores. Food Available and Food Present scores, but not Food Tasted, were also significantly higher among overweight participants. CONCLUSIONS: Higher hedonic hunger and CD were associated with higher SBP and all adiposity measures. Overweight participants had higher hedonic hunger in the context of ready availability and physical presence of highly palatable foods. Lower self-control was weakly correlated with higher central adiposity; lower impulsivity and restraint were weakly correlated with higher visceral adiposity. These findings have provided some insights into the cognitive factors underlying adiposity.

Adiposity, Body Composition Measures, and Breast Cancer Risk in Korean Premenopausal Women.

Objective: To investigate the association between body composition parameters and breast cancer (BC) risk in premenopausal women. Design, Setting, and Participants: Prospective cohort study using data from the Kangbuk Samsung Cohort Study. Participants were women aged 20 to 54 years who were enrolled from 2011 to 2019 and followed up for BC development until December 31, 2020. Data were analyzed from June to August 2023. Exposures: Trained nurses conducted anthropometric measurements and assessed body composition using segmental bioelectric impedance analysis. The analysis encompassed adiposity measures such as body mass index (BMI), waist circumference, and body composition parameters, including muscle mass, fat mass, ratio of muscle mass to weight, ratio of fat mass to weight, and fat mass index. Main outcomes and measures: Adjusted hazard ratios (aHR) for BC during the follow-up period. Results: Among 125 188 premenopausal women, the mean (SD) age was 34.9 (6.3) years. During a mean (range) follow-up of 6.7 (0.5-9.9) years, 1110 incident BC cases were identified. The mean (SD) BMI and waist circumference were 21.6 (3.1) and 75.3 (8.2) cm, respectively. Higher BMI and waist circumference were associated with decreased risk, with an aHR of 0.89 (95% CI, 0.84-0.95) per SD increase in BMI and 0.92 (95% CI, 0.86-0.98) per SD increase in waist circumference. A higher ratio of fat mass to weight was associated with decreased BC risk (aHR, 0.92; 95% CI, 0.86-0.99 per SD increase), whereas the opposite trend was observed for the ratio of muscle mass to weight, with an aHR of 1.08 (95% CI, 1.02-1.15) per SD increase. The results remained consistent even after additional adjustments for height in the model. The fat mass index was also inversely associated with BC risk, with an HR of 0.90 (95% CI, 0.85-0.97) per SD increase. Conclusions and Relevance: In this cohort study of premenopausal women, a higher level of adiposity, represented by increased BMI, waist circumference, and fat mass, was consistently associated with decreased breast cancer risk. Conversely, muscle mass and its ratio to weight displayed opposite or inconsistent patterns. These findings suggest an inverse association between excess adiposity and the risk of BC in premenopausal women, confirming earlier findings that BMI is an indirect measure of adiposity.

Association of longitudinal trajectories of general and abdominal adiposity during middle age with mental health and well-being in late life: A prospective analysis.

Single measures of adiposity markers, such as body mass index (BMI) and waist circumference (WC), are associated with adverse mental health outcomes; however, long-term patterns of adiposity and their health effects remain unclear. The current study assessed adiposity trajectories during a 14-year span beyond middle age and their relevance to mental well-being in late life, and the contribution of genetic and lifestyle factors to the trajectories. Based on a nationally representative sample with longitudinal anthropometric measures, adiposity trajectories were identified by latent mixture modeling, and logistic regression model was used to estimate their associations with mental well-being, with adjustment for confounders. Of the 3491 eligible participants included (mean [SD] age, 69.5 [8.9] years), five discrete BMI and four WC trajectory patterns were identified over 14 years. Compared with the low-stable BMI group (range, 22.8 to 22.9 kg/m²; representing stable healthy body weight), the high-stable group (range, 34.3 to 35.4 kg/m²; stable obese) was associated with increased risk of depression (odds ratio [OR], 1.63; 95 % CI, 1.28-2.07) and low subjective well-being (OR, 1.35; 95 % CI, 1.02-1.79). Compared with the low-stable WC group (range, 75 to 79 cm healthy WC), the high-increasing group (range, 114 to 121 cm) was associated with increased risk of depression (odds ratio [OR], 1.64; 95 % CI, 1.19-2.25) and low well-being (OR, 1.48; 95 % CI, 1.01-2.16). The adiposity trajectories, especially the high-stable/increasing groups, were driven by genetic factors in a dose-response manner, whereas the high/moderate-increasing groups were also behaviorally related. This longitudinal cohort study reveals that stably high trajectory patterns of central and general adiposity during middle age were associated with higher risk of depression and low well-being in late life. The findings indicate the importance of weight management beyond middle age, such as adherence to a healthy lifestyle, in promoting mental health and well-being.

The complex associations between adiposity, fitness, mental wellbeing and neurocognitive function after exercise: A randomized crossover trial in preadolescent children.

The aim of the present study was to examine the associations of adiposity and fitness on the preadolescent brain's response to acute exercise. In a sample of 58 children (ages 8-10; 19 females), demographic measures of age, sex, IQ, puberty, and socioeconomic status were considered. Children participated in a randomized crossover study, whereby they completed two different interventions; seated rest or treadmill walking, counterbalanced across participants. Associations between adiposity measures (standardized body mass index [BMI-Z], whole body percent fat [%Fat], visceral adipose tissue [VAT]), cardiorespiratory fitness measures (VO2max and Fat-Free VO2) were assessed on self-reported measures of mental wellbeing, and cognitive performance (response accuracy, reaction time) and neuroelectric (P3 amplitude and latency) indices of a Go/NoGo task following both exercise and rest interventions. Higher adiposity (whole-body percent fat, BMI-Z) was associated with higher trait anxiety (P's≤0.05) and disordered eating (P's≤0.05) scores. Higher fitness (VO2max) was associated with lower childhood depression scores (P=0.02). Regression analyses yielded specific post-exercise neurocognitive associations with adiposity-related (VAT, BMI-Z), and fitness-related (FF-VO2) outcomes, after controlling for post-rest neurocognitive outcomes. VAT was positively associated with post-exercise P3 ERP Latency for the Go task (P≤0.001); BMI-Z was negatively associated with P3 ERP amplitudes for the Go task (P's≤0.005); FF-VO2 was negatively associated with P3 ERP latency for the Go/NoGo task (P's≤0.05), and positively associated with NoGo task accuracy (P≤0.001). Overall, adiposity and fat-free fitness measures yield sensitive and differential associations with neurocognitive performance after exercise and after rest interventions.

The potential mechanisms underlying the modulating effect of perirenal adipose tissue on hypertension: Physical compression, paracrine, and neurogenic regulation.

Hypertension, a prevalent global cardiovascular disease, affects approximately 45.4 % of adults worldwide. Despite advances in therapy, hypertension continues to pose a significant health risk due to inadequate management. It has been established that excessive adiposity contributes majorly to hypertension, accounting for 65 to 75 % of primary cases. Fat depots can be categorised into subcutaneous and visceral adipose tissue based on anatomical and physiological characteristics. The metabolic impact and the risk of hypertension are determined more significantly by visceral fat. Perirenal adipose tissue (PRAT), a viscera enveloping the kidney, is known for its superior vascularisation and abundant innervation. Although traditionally deemed as a mechanical support tissue, recent studies have indicated its contributing potential to hypertension. Hypertensive patients tend to have increased PRAT thickness compared to those without, and there is a positive correlation between PRAT thickness and elevated systolic blood pressure. This review encapsulates the anatomical characteristics and biogenesis of PRAT. We provide an overview of the potential mechanisms where PRAT may modulate blood pressure, including physical compression, paracrine effects, and neurogenic regulation. PRAT has become a promising target for hypertension management, and continuous effort is required to further explore the underlying mechanisms.

Neurodevelopmental Programming of Adiposity: Contributions to Obesity Risk.

This review analyzes the published evidence regarding maternal factors that influence the developmental programming of long-term adiposity in humans and animals via the central nervous system (CNS). We describe the physiological outcomes of perinatal underfeeding and overfeeding and explore potential mechanisms that may mediate the impact of such exposures on the development of feeding circuits within the CNS-including the influences of metabolic hormones and epigenetic changes. The perinatal environment, reflective of maternal nutritional status, contributes to the programming of offspring adiposity. The in utero and early postnatal periods represent critically sensitive developmental windows during which the hormonal and metabolic milieu affects the maturation of the hypothalamus. Maternal hyperglycemia is associated with increased transfer of glucose to the fetus driving fetal hyperinsulinemia. Elevated fetal insulin causes increased adiposity and consequently higher fetal circulating leptin concentration. Mechanistic studies in animal models indicate important roles of leptin and insulin in central and peripheral programming of adiposity, and suggest that optimal concentrations of these hormones are critical during early life. Additionally, the environmental milieu during development may be conveyed to progeny through epigenetic marks and these can potentially be vertically transmitted to subsequent generations. Thus, nutritional and metabolic/endocrine signals during perinatal development can have lifelong (and possibly multigenerational) impacts on offspring body weight regulation.

Grip strength positively correlates with blood pressure in individuals with abnormal adiposity.

Although strong positive correlations exist between grip strength and cardiovascular health, the association between grip strength and blood pressure (BP) is less clear. In this regard, a more precise relationship between grip strength and BP may be revealed by considering adiposity. We examined the association between grip strength and BP in 9424 individuals aged 18-92 years, while controlling for or stratifying by body mass index (BMI) or body fat (BF)%. Grip strength, BP and BF% were determined using dynamometry, sphygmomanometry and dual-energy x-ray absorptiometry. Overall, those with elevated BP had greater grip strength than those with normal BP (39.17 kg vs 38.38 kg, p < 0.001); however, following stratification this was only observed in overweight or obese individuals (42.08 kg vs 41.10 kg, p = 0.003 and 41.34 kg vs 40.03 kg, p = 0.033), and those within the highest BF% tertile (37.95 kg vs 36.52 kg, p < 0.001). Overall, higher grip strength was associated with an increased odds for elevated BP (OR = 1.014, 95% CI = 1.004-1.024, p = 0.004); however, after stratification the increased odds was only observed in overweight or obese individuals (OR = 1.025, 95% CI = 1.010-1.039, p < 0.001 and OR = 1.018, 95% CI = 1.004-1.031, p = 0.010), and those within the highest BF% tertile (OR = 1.036, 95% CI = 1.022-1.051, p < 0.001). Individuals with low grip strength and high BF% had lower odds for elevated BP (OR = 0.514, 95% CI = 0.341-0.775, p = 0.002), whereas those with low grip strength and low BF% had higher odds for elevated BP (OR = 2.162, 95% CI = 1.026-4.555, p = 0.043). Our findings show that higher grip strength is related to higher BP in overweight or obese individuals, or those with a high BF%. Having a BMI < 25 kg/m2 or lower BF% may neutralise this association.

Circadian misalignment impacts the association of visceral adiposity with metabolic syndrome in adolescents.

STUDY OBJECTIVES: Although insufficient sleep is a risk factor for metabolic syndrome (MetS), the circadian timing of sleep (CTS) is also involved in cardiac and metabolic regulation. We examined whether delays and deviations in the sleep midpoint (SM), a measure of CTS, modify the association between visceral adipose tissue (VAT) and MetS in adolescents. METHODS: We evaluated 277 adolescents (median 16 years) who had at least 5 nights of at-home actigraphy (ACT), in-lab polysomnography (PSG), dual-energy X-ray absorptiometry (DXA) scan, and MetS score data. Sleep midpoint (SM), sleep irregularity (SI), and social jetlag (SJL) were examined as effect modifiers of the association between VAT and MetS, including waist circumference, blood pressure, insulin resistance, triglycerides, and cholesterol. Linear regression models adjusted for demographics, ACT-sleep duration, ACT-sleep variability, and PSG-apnea-hypopnea index. RESULTS: The association between VAT and MetS was significantly stronger (p-values for interactions < 0.001) among adolescents with a schooldays SM later than 4:00 (2.66 [0.30] points increase in MetS score), a SI higher than 1 hour (2.49 [0.30]) or a SJL greater than 1.5 hours (2.15 [0.36]), than in those with an earlier SM (<3:00; 1.76 [0.28]), lower SI (<30 minutes; 0.98 [0.70]), or optimal SJL (<30 minutes; 1.08 [0.45]). CONCLUSIONS: A delayed sleep phase, an irregular sleep-wake cycle, and greater social jetlag on schooldays identified adolescents in whom VAT had a stronger association with MetS. Circadian misalignment is a risk factor that enhances the impact of visceral obesity on cardiometabolic morbidity and should be a target of preventative strategies in adolescents.

Brief Report: Relationship Between Adiposity and Biomarkers of Aging and Frailty Among Adults Aging With HIV.

BACKGROUND: This study examined the relationships among adiposity, handgrip, physical function, inflammation (ie, senescence-associated secretory phenotype chemokines as biomarkers of aging and frailty), and sex hormones in aging people with HIV. METHODS: This cross-sectional exploratory study included 150 people with HIV aged ≥40 years (67.3% of participants were male). Our measures included (1) body mass index and waist circumference as measures of adiposity; (2) handgrip as a measure of muscle strength; (3) short physical performance battery as a measure of physical function; (4) interleukin-6, tumor necrosis factor alpha receptor II, high sensitivity C-reactive protein, C-X-C motif chemokine 10, and C-X3-C motif chemokine ligand 1 also known as fractalkine as senescence-associated secretory phenotype chemokines; and (5) free testosterone, estradiol, sex hormone-binding globulin, and dehydroepiandrosterone as sex hormones. Quantile regression analyses were used to identify relationships among inflammatory markers and hormones with age, adiposity, handgrip, and physical function. RESULTS: Overall, 74% (n = 111) of participants were classified as overweight or obese and 53.3% (n = 80) presented with abdominal obesity. After controlling for age and sex, body mass index was positively associated with estradiol (ß = 0.043, P < 0.01), and waist circumference was positively associated with high sensitivity C-reactive protein (ß = 2.151, P < 0.01). After controlling for sex, age was positively associated with C-X-C motif chemokine 10 (ß = 0.024, P = 0.03) and tumor necrosis factor alpha receptor II (ß = 2.205, P = 0.01). After controlling for age and sex, short physical performance battery was negatively associated with dehydroepiandrosterone (ß = -0.004, P = 0.01); no statistically significant associations were observed for handgrip. CONCLUSION: Adiposity levels and aging were associated with inflammation (ie, C-X-C motif chemokine 10, tumor necrosis factor alpha receptor II, and high sensitivity C-reactive protein) among people with HIV aged 40 years and older.

Associations of general and central adiposity with hypertension and cardiovascular disease among South Asian populations: a systematic review and meta-analysis.

BACKGROUND: The relevance of measures of general and central adiposity for cardiovascular disease (CVD) risks in populations of European descent is well established. However, it is less well characterised in South Asian populations, who characteristically manifest larger waist circumferences (WC) for equivalent body mass index (BMI). This systematic review and meta-analysis provide an overview of the literature on the association of different anthropometric measures with CVD risk among South Asians. METHODOLOGY: MEDLINE and Embase were searched from 1990 to the present for studies in South Asian populations investigating associations of two or more adiposity measures with CVD. Random-effects meta-analyses were conducted on the associations of BMI, WC and waist-to-hip ratio (WHR) with blood pressure, hypertension and CVD. Quality assessment was performed using the Newcastle-Ottawa scale. RESULTS: Titles and abstracts were screened for 7327 studies, yielding 147 full-text reviews. The final sample (n=30) included 2 prospective, 5 case-control and 23 cross-sectional studies. Studies reported generally higher risks of hypertension and CVD at higher adiposity levels. The pooled mean difference in systolic blood pressure (SBP) per 5 kg/m2 higher BMI was 3 mmHg (2.90 (95% CI 1.30 to 4.50)) and 6 mmHg (6.31 (95% CI 4.81 to 7.81) per 13 cm larger WC. The odds ratio (OR) of hypertension per 5 kg/m2 higher BMI was 1.33 (95% CI 1.18 to 1.51), 1.45 (95% CI 1.05 to 1.98) per 13 cm larger WC and 1.22 (95% CI 1.04 to 1.41) per 0.1-unit larger WHR. Pooled risk of CVD for BMI-defined overweight versus healthy-weight was 1.65 (95% CI 1.55 to 1.75) and 1.48 (95% CI 1.21 to 1.80) and 2.51 (95% CI 0.94 to 6.69) for normal versus large WC and WHR, respectively. Study quality was average with significant heterogeneity. CONCLUSIONS: Measures of both general and central adiposity had similar, strong positive associations with the risk of CVD in South Asians. Larger prospective studies are required to clarify which measures of body composition are more informative for targeted CVD primary prevention in this population.

Plasma IGFBP-2 levels reveal heterogeneity in hepatic fat content in adults with excess visceral adiposity.

Lay summary: Obesity is frequently accompanied by a fatty liver. However, some individuals with high abdominal fat levels nevertheless have low levels of liver fat. Reasons for such discordant phenotypes are unclear. In this paper, we report that among asymptomatic individuals with high levels of visceral fat, low concentrations of IGFBP-2 in the circulation were associated with significantly higher hepatic fat content compared to those with high IGFBP-2 levels. We conclude that quantification of plasma IGFBP-2 concentrations may be useful to identify the early risk for liver fat accumulation in apparently healthy individuals without cardiovascular symptoms. Aim/hypothesis: Although excess visceral adiposity (VAT) is generally associated with increased liver fat (LF), recent evidence has revealed heterogeneity in LF content among adults with visceral obesity, potentially contributing to specific differences in cardiometabolic outcomes. Reasons for such discordant VAT-LF phenotypes are largely unknown. The present study aimed at assessing whether circulating levels of insulin growth-factor binding protein-2 (IGFBP-2) could be a useful biomarker in the identification of heterogenous and discordant VAT-LF phenotypes. Methods: A sample of 308 middle-aged Caucasian apparently healthy men and women without cardiovascular symptoms were studied for the present cross-sectional analyses. Fasting plasma glucose and lipid levels were assessed and an oral glucose tolerance test was performed. Hepatic fat fraction (HFF) was measured using magnetic resonance spectroscopy whereas VAT was assessed by magnetic resonance imaging. Plasma IGFBP-2 levels were quantified by ELISA. Participants were then classified on the basis of median VAT (81 mL) and IGFBP-2 levels (233 ng/mL). Results: Individuals with high levels of VAT were characterized by higher waist circumference, lower insulin sensitivity, as well as by higher plasma triglyceride and lower HDL-cholesterol levels. Plasma IGFBP-2 levels were inversely correlated with HFF (r = -0.39, p < 0.0001). Among men and women with high levels of VAT, those with low levels of IGFBP-2 had significantly higher HFF (7.5 ± 0.7%), compared to participants with high IGFBP-2 concentrations (3.2 ± 0.5%, p < 0.0001). Conclusion: In the presence of excess VAT, high IGFBP-2 concentrations are associated with low levels of LF. Although additional studies will be necessary to establish causality and further clarify the clinical implications of these observations, these findings are concordant with a novel function of IGFBP-2 in modulating susceptibility to non-alcoholic fatty liver disease (NAFLD) in the presence of visceral obesity.

A protein kinase C α and ß inhibitor blunts hyperphagia to halt renal function decline and reduces adiposity in a rat model of obesity-driven type 2 diabetes.

Type 2 diabetes (T2D) and its complications can have debilitating, sometimes fatal consequences for afflicted individuals. The disease can be difficult to control, and therapeutic strategies to prevent T2D-induced tissue and organ damage are needed. Here we describe the results of administering a potent and selective inhibitor of Protein Kinase C (PKC) family members PKCα and PKCß, Cmpd 1, in the ZSF1 obese rat model of hyperphagia-induced, obesity-driven T2D. Although our initial intent was to evaluate the effect of PKCα/ß inhibition on renal damage in this model setting, Cmpd 1 unexpectedly caused a marked reduction in the hyperphagic response of ZSF1 obese animals. This halted renal function decline but did so indirectly and indistinguishably from a pair feeding comparator group. However, above and beyond this food intake effect, Cmpd 1 lowered overall animal body weights, reduced liver vacuolation, and reduced inguinal adipose tissue (iWAT) mass, inflammation, and adipocyte size. Taken together, Cmpd 1 had strong effects on multiple disease parameters in this obesity-driven rodent model of T2D. Further evaluation for potential translation of PKCα/ß inhibition to T2D and obesity in humans is warranted.

Maternal Prenatal Factors and Child Adiposity in Associations with Cardiometabolic Risk Factors in Term-Born Chinese Children at the Age of 2 Years.

Early growth has long-lasting associations with adult metabolic health. However, the association of adiposity with cardiometabolic risk factors in toddlers remains poorly understood. This study aimed to examine the association of maternal prenatal factors and child adiposity with child cardiometabolic risk factors among boys and girls aged 2 years. This was a birth cohort study of 549 term-born children in Shanghai, China, with follow-up data at the age of 2-years. Child anthropometric and adiposity measurements included weight, length, and skinfold thickness (triceps, subscapular, and abdominal). Child cardiometabolic risk factors included random morning plasma glucose, serum insulin, lipids, and systolic and diastolic blood pressure (SBP, DBP). At 2 years, overweight/obesity (weight-for-length z score, ZWFL > 2) was associated with 12.6 (95%CI 7.7, 17.4) mmHg higher SBP, and 7.9 (4.1, 11.8) mmHg higher DBP in boys, with similar results observed in girls. Maternal hypertensive disorders of pregnancy were associated with 3.0 (0.1, 5.8) higher SBP, 3.17 (0.90, 5.44) mmHg higher DBP, 0.24 (0.01,0.47) mmol/L higher plasma glucose, and 0.26 (0.01,0.51) mmol/L higher serum triglycerides after adjustment for child age, sex, and ZWFL. Maternal hypertensive disorders of pregnancy and child overweight/obesity were associated with higher SBP and DBP at the age of 2 years.

Intestinal permeability and peripheral immune cell composition are altered by pregnancy and adiposity at mid- and late-gestation in the mouse.

It is clear that the gastrointestinal tract influences metabolism and immune function. Most studies to date have used male test subjects, with a focus on effects of obesity and dietary challenges. Despite significant physiological maternal adaptations that occur across gestation, relatively few studies have examined pregnancy-related gut function. Moreover, it remains unknown how pregnancy and diet can interact to alter intestinal barrier function. In this study, we investigated the impacts of pregnancy and adiposity on maternal intestinal epithelium morphology, in vivo intestinal permeability, and peripheral blood immunophenotype, using control (CTL) and high-fat (HF) fed non-pregnant female mice and pregnant mice at mid- (embryonic day (E)14.5) and late (E18.5) gestation. We found that small intestine length increased between non-pregnant mice and dams at late-gestation, but ileum villus length, and ileum and colon crypt depths and goblet cell numbers remained similar. Compared to CTL-fed mice, HF-fed mice had reduced small intestine length, ileum crypt depth and villus length. Goblet cell numbers were only consistently reduced in HF-fed non-pregnant mice. Pregnancy increased in vivo gut permeability, with a greater effect at mid- versus late-gestation. Non-pregnant HF-fed mice had greater gut permeability, and permeability was also increased in HF-fed pregnant dams at mid but not late-gestation. The impaired maternal gut barrier in HF-fed dams at mid-gestation coincided with changes in maternal blood and bone marrow immune cell composition, including an expansion of circulating inflammatory Ly6Chigh monocytes. In summary, pregnancy has temporal effects on maternal intestinal structure and barrier function, and on peripheral immunophenotype, which are further modified by HF diet-induced maternal adiposity. Maternal adaptations in pregnancy are thus vulnerable to excess maternal adiposity, which may both affect maternal and child health.

An adiposity force induces obesity in humans independently of a normal energy balance system-a thought experiment.

Obesity in humans represents a cumulative retention of a tiny fraction of total energy intake as fat, which is accompanied by growth of the metabolically active, energy-demanding, lean body mass. Since the energy balance regulation operates irrespective of the excess fat storage, availability of the required energy supplies is a permissive condition for obesity development. It occurs predominantly among people genetically predisposed and/or living with social or mental challenges. I propose a theory in which the body responds to social disruptions as threats of a future lack of food by an adiposity force building a reserve of energy independent of the regulation of the energy balance. It is based on the assumption that our evolutionary development required collaboration in gathering and sharing of food, combined with precautionary measures against anticipated failing food supplies. Social challenges are perceived as such threats, which activate the adiposity force through the brain to instigate the growth of fat and lean mass by neuro-hormonal signalling. If both perceived social threats and food abundance continue, the adiposity force pushes the fat accretion process to continue without inhibition by feedback signals from the fat mass, eventually leading to more obesity, and more so among the genetically predisposed. This article is part of a discussion meeting issue 'Causes of obesity: theories, conjectures and evidence (Part I)'.

Cardiovascular fitness is associated with child adiposity at 5 years of age: findings from the ROLO longitudinal birth cohort study.

BACKGROUND: Cardiovascular fitness is strongly linked with metabolic risk; however, research is limited in preschool children. Although there is currently no simple validated measure of fitness in preschool children, heart rate recovery has been highlighted as an easily accessible and non-invasive predictor of cardiovascular risk in school-aged children and adolescents. We aimed to investigate whether heart rate recovery was associated with adiposity and blood pressure in 5-year-olds. STUDY DESIGN: This is a secondary analysis of 272 5-year-olds from the ROLO (Randomised cOntrol trial of LOw glycaemic index diet in pregnancy to prevent recurrence of macrosomia) Kids study. Three-minute step tests were completed by 272 participants to determine heart rate recovery duration. Body mass index (BMI), circumferences, skinfold thickness, heart rate, and blood pressure were collected. Independent t-tests, Mann-Whitney U, and Chi-square tests were used to compare participants. Linear regression models examined associations between heart rate recovery and child adiposity. Confounders included child sex, age at study visit, breastfeeding, and perceived effort in the step test. RESULTS: The median (IQR) age at the study visit was 5.13 (0.16) years. 16.2% (n = 44) had overweight and 4.4% (n = 12) had obesity based on their BMI centile. Boys had a quicker mean (SD) heart rate recovery after the step test than girls (112.5 (47.7) seconds vs. 128.8 (62.5) seconds, p = 0.02). Participants with a slower recovery time (> 105 s) had higher median (IQR) sum of skinfolds (35.5 (11.8) mm vs. 34.0 (10.0) mm, p = 0.02) and median (IQR) sum of subscapular and triceps skinfold (15.6 (4.4) mm vs. 14.4 (4.0) mm, p = 0.02) compared to participants with a quicker recovery time. After adjusting for confounders (child sex, age at study visit, breastfeeding, effort in the step test), linear regression analyses revealed heart rate recovery time after stepping was positively associated with sum of skinfolds (B = 0.034, 95% CI: 0.01, 0.06, p = 0.007). CONCLUSION: Child adiposity was positively associated with heart rate recovery time after the step test. A simple stepping test could be used as a non-invasive and inexpensive fitness tool in 5-year-olds. Additional research is needed to validate the ROLO Kids step test in preschool children.

Increase in skeletal muscular adiposity and cognitive decline in a biracial cohort of older men and women.

BACKGROUND: Obesity and loss of muscle mass are emerging as risk factors for dementia, but the role of adiposity infiltrating skeletal muscles is less clear. Skeletal muscle adiposity increases with older age and especially among Black women, a segment of the US population who is also at higher risk for dementia. METHODS: In 1634 adults (69-79 years, 48% women, 35% Black), we obtained thigh intermuscular adipose tissue (IMAT) via computerized tomography at Years 1 and 6, and mini-mental state exam (3MS) at Years 1, 3, 5, 8 and 10. Linear mixed effects models tested the hypothesis that increased IMAT (Year 1-6) would be associated with 3MS decline (Year 5-10). Models were adjusted for traditional dementia risk factors at Year 1 (3MS, education, APOe4 allele, diabetes, hypertension, and physical activity), with interactions between IMAT change by race or sex. To assess the influence of other muscle and adiposity characteristics, models accounted for change in muscle strength, muscle area, body weight, abdominal subcutaneous and visceral adiposity, and total body fat mass (all measured in Years 1 and 6). Models were also adjusted for cytokines related to adiposity: leptin, adiponectin, and interleukin-6. RESULTS: Thigh IMAT increased by 4.85 cm2 (Year 1-6) and 3MS declined by 3.20 points (Year 6-10). The association of IMAT increase with 3MS decline was statistically significant: an IMAT increase of 4.85 cm2 corresponded to a 3MS decline of an additional 3.60 points (p < 0.0001), indicating a clinically important change. Interactions by race and sex were not significant. CONCLUSIONS: Clinicians should be aware that regional adiposity accumulating in the skeletal muscle may be an important, novel risk factor for cognitive decline in Black and White participants independent of changes to muscle strength, body composition and traditional dementia risk factors.

Philosophically, is obesity really a disease?

The question of whether obesity should be regarded as a disease remains controversial. One source of controversy can be addressed by distinguishing between two ways in which the word "obesity" is used. In medicine, the word "obesity" now typically refers to some or all of a set of interrelated dysfunctions of metabolism, adipose tissue, and dietary intake regulation. In other contexts, such as government-funded public education programs, the word "obesity" refers to a body mass index (BMI) category taken to indicate excess body fat. The result is that when medical experts say, "Obesity is a disease," the majority of outside medicine inevitably takes this to mean "being fat is a disease." In order to address this ambiguity, we apply key philosophical accounts of disease to the two different senses of "obesity." We draw two major conclusions: First, although obesity as understood in clinical medicine meets the criteria to be considered a disease, obesity as defined by BMI does not. Second, adequately addressing this disease requires us to distinguish it clearly and unambiguously from high BMI. Making this distinction would help both the public and policymakers to better understand the disease of obesity, facilitating advances in both prevention and treatment.

Senescent immune cells accumulation promotes brown adipose tissue dysfunction during aging.

Brown adipose tissue (BAT)-mediated thermogenesis declines with age. However, the underlying mechanism remains unclear. Here we reveal that bone marrow-derived pro-inflammatory and senescent S100A8+ immune cells, mainly T cells and neutrophils, invade the BAT of male rats and mice during aging. These S100A8+ immune cells, coupled with adipocytes and sympathetic nerves, compromise axonal networks. Mechanistically, these senescent immune cells secrete abundant S100A8 to inhibit adipose RNA-binding motif protein 3 expression. This downregulation results in the dysregulation of axon guidance-related genes, leading to impaired sympathetic innervation and thermogenic function. Xenotransplantation experiments show that human S100A8+ immune cells infiltrate mice BAT and are sufficient to induce aging-like BAT dysfunction. Notably, treatment with S100A8 inhibitor paquinimod rejuvenates BAT axon networks and thermogenic function in aged male mice. Our study suggests that targeting the bone marrow-derived senescent immune cells presents an avenue to improve BAT aging and related metabolic disorders.

Genetically prolonged beige fat in male mice confers long-lasting metabolic health.

A potential therapeutic target to curb obesity and diabetes is thermogenic beige adipocytes. However, beige adipocytes quickly transition into white adipocytes upon removing stimuli. Here, we define the critical role of cyclin dependent kinase inhibitor 2A (Cdkn2a) as a molecular pedal for the beige-to-white transition. Beige adipocytes lacking Cdkn2a exhibit prolonged lifespan, and male mice confer long-term metabolic protection from diet-induced obesity, along with enhanced energy expenditure and improved glucose tolerance. Mechanistically, Cdkn2a promotes the expression and activity of beclin 1 (BECN1) by directly binding to its mRNA and its negative regulator BCL2 like 1 (BCL2L1), activating autophagy and accelerating the beige-to-white transition. Reactivating autophagy by pharmacological or genetic methods abolishes beige adipocyte maintenance induced by Cdkn2a ablation. Furthermore, hyperactive BECN1 alone accelerates the beige-to-white transition in mice and human. Notably, both Cdkn2a and Becn1 exhibit striking positive correlations with adiposity. Hence, blocking Cdkn2a-mediated BECN1 activity holds therapeutic potential to sustain beige adipocytes in treating obesity and related metabolic diseases.