-
1.
Anthropometry, body shape in early-life and risk of premenopausal breast cancer among Latin American women: results from the PRECAMA study.
His, M, Biessy, C, Torres-Mejía, G, Ángeles-Llerenas, A, Alvarado-Cabrero, I, Sánchez, GI, Borrero, M, Porras, C, Rodriguez, AC, Garmendia, ML, et al
Scientific reports. 2020;(1):2294
Abstract
Cumulating evidence in Caucasian women suggests a positive association between height and premenopausal breast cancer risk and a negative association with overall adiposity; however data from Latin America are scarce. We investigated the associations between excess adiposity, body shape evolution across life, and risk of premenopausal breast cancer among 406 cases (women aged 20-45) and 406 matched population-based controls from Chile, Colombia, Costa Rica, and Mexico. Negative associations between adult adiposity and breast cancer risk were observed in adjusted models (body mass index (BMI): Odds ratio (OR) per 1 kg/m2 = 0.93; 95% confidence interval = 0.89-0.96; waist circumference (WC): OR per 10 cm = 0.81 (0.69-0.96); hip circumference (HC): OR per 10 cm = 0.80 (0.67-0.95)). Height and leg length were not associated with risk. In normal weight women (18.5 ≤ BMI < 25), women with central obesity (WC > 88 cm) had an increased risk compared to women with normal WC (OR = 3.60(1.47-8.79)). Residuals of WC over BMI showed positive associations when adjusted for BMI (OR per 10 cm = 1.38 (0.98-1.94)). Body shape at younger ages and body shape evolution were not associated with risk. No heterogeneity was observed by receptor status. In this population of Latin American premenopausal women, different fat distributions in adulthood were differentially associated with risk of breast cancer.
-
2.
Individual Response to Standardized Exercise: Total and Abdominal Adipose Tissue.
Brennan, AM, Day, AG, Cowan, TE, Clarke, GJ, Lamarche, B, Ross, R
Medicine and science in sports and exercise. 2020;(2):490-497
Abstract
PURPOSE (1) Determine the effect of exercise amount and intensity on the proportion of individuals for whom the adipose tissue (AT) response is above the minimal clinically important difference (MCID); and (2) Examine whether clinically meaningful anthropometric changes reflect individual AT responses above the MCID. METHODS Men (n = 41) and women (n = 62) (52.7 ± 7.6 yr) were randomized to control (n = 20); low amount low intensity (n = 24); high amount low intensity (n = 30); and high amount high intensity (n = 29) treadmill exercise for 24 wk. The AT changes were measured by MRI. 90% confidence intervals for each individual's observed response were calculated as the observed score ±1.64 × TE (technical error of measurement). RESULTS For visceral AT, HAHI and HALI had a greater proportion of individuals whose AT change and 90% confidence interval were beyond the MCID compared to controls (P < 0.006). For all other AT depots, all exercise groups had significantly more individuals whose changes were beyond the MCID compared with controls. Of those who achieved a waist circumference or body weight reduction ≥ the MCID, 76% to 93% achieved abdominal, abdominal subcutaneous, and visceral AT changes ≥ the MCID. CONCLUSIONS Increasing exercise amount and/or intensity may increase the proportion of individuals who achieve clinically meaningful visceral AT reductions. Waist circumference or body weight changes beyond a clinically meaningful threshold are predictive of clinically meaningful abdominal adiposity changes.
-
3.
Adiposity, metabolites, and colorectal cancer risk: Mendelian randomization study.
Bull, CJ, Bell, JA, Murphy, N, Sanderson, E, Davey Smith, G, Timpson, NJ, Banbury, BL, Albanes, D, Berndt, SI, Bézieau, S, et al
BMC medicine. 2020;(1):396
Abstract
BACKGROUND Higher adiposity increases the risk of colorectal cancer (CRC), but whether this relationship varies by anatomical sub-site or by sex is unclear. Further, the metabolic alterations mediating the effects of adiposity on CRC are not fully understood. METHODS We examined sex- and site-specific associations of adiposity with CRC risk and whether adiposity-associated metabolites explain the associations of adiposity with CRC. Genetic variants from genome-wide association studies of body mass index (BMI) and waist-to-hip ratio (WHR, unadjusted for BMI; N = 806,810), and 123 metabolites from targeted nuclear magnetic resonance metabolomics (N = 24,925), were used as instruments. Sex-combined and sex-specific Mendelian randomization (MR) was conducted for BMI and WHR with CRC risk (58,221 cases and 67,694 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium, Colorectal Cancer Transdisciplinary Study, and Colon Cancer Family Registry). Sex-combined MR was conducted for BMI and WHR with metabolites, for metabolites with CRC, and for BMI and WHR with CRC adjusted for metabolite classes in multivariable models. RESULTS In sex-specific MR analyses, higher BMI (per 4.2 kg/m2) was associated with 1.23 (95% confidence interval (CI) = 1.08, 1.38) times higher CRC odds among men (inverse-variance-weighted (IVW) model); among women, higher BMI (per 5.2 kg/m2) was associated with 1.09 (95% CI = 0.97, 1.22) times higher CRC odds. WHR (per 0.07 higher) was more strongly associated with CRC risk among women (IVW OR = 1.25, 95% CI = 1.08, 1.43) than men (IVW OR = 1.05, 95% CI = 0.81, 1.36). BMI or WHR was associated with 104/123 metabolites at false discovery rate-corrected P ≤ 0.05; several metabolites were associated with CRC, but not in directions that were consistent with the mediation of positive adiposity-CRC relations. In multivariable MR analyses, associations of BMI and WHR with CRC were not attenuated following adjustment for representative metabolite classes, e.g., the univariable IVW OR for BMI with CRC was 1.12 (95% CI = 1.00, 1.26), and this became 1.11 (95% CI = 0.99, 1.26) when adjusting for cholesterol in low-density lipoprotein particles. CONCLUSIONS Our results suggest that higher BMI more greatly raises CRC risk among men, whereas higher WHR more greatly raises CRC risk among women. Adiposity was associated with numerous metabolic alterations, but none of these explained associations between adiposity and CRC. More detailed metabolomic measures are likely needed to clarify the mechanistic pathways.
-
4.
Adiposity and estrogen receptor-positive, postmenopausal breast cancer risk: Quantification of the mediating effects of fasting insulin and free estradiol.
Dashti, SG, Simpson, JA, Karahalios, A, Viallon, V, Moreno-Betancur, M, Gurrin, LC, MacInnis, RJ, Lynch, BM, Baglietto, L, Morris, HA, et al
International journal of cancer. 2020;(6):1541-1552
-
-
Free full text
-
Abstract
Adiposity increases estrogen receptor (ER)-positive postmenopausal breast cancer risk. While mechanisms underlying this relationship are uncertain, dysregulated sex-steroid hormone production and insulin signaling are likely pathways. Our aim was to quantify mediating effects of fasting insulin and free estradiol in the adiposity and ER-positive postmenopausal breast cancer association. We used data from a case-cohort study of sex hormones and insulin signaling nested within the Melbourne Collaborative Cohort Study. Eligible women, at baseline, were not diagnosed with cancer, were postmenopausal, did not use hormone therapy and had no history of diabetes or diabetes medication use. Women with ER-negative disease or breast cancer diagnosis within the first follow-up year were excluded. We analyzed the study as a cumulative sampling case-control study with 149 cases and 1,029 controls. Missing values for insulin and free estradiol were multiply imputed with chained equations. Interventional direct (IDE) and indirect (IIE) effects were estimated using regression-based multiple-mediator approach. For women with body mass index (BMI) >30 kg/m2 compared to women with BMI 18.5-25 kg/m2 , the risk ratio (RR) of breast cancer was 1.75 (95% confidence interval [CI] 1.05-2.91). The estimated IDE (RR) not through the mediators was 1.03 (95% CI 0.43-2.48). Percentage mediated effect through free estradiol was 72% (IIE-RR 1.56; 95% CI 1.11-2.19). There was no evidence for an indirect effect through insulin (IIE-RR 1.12; 95% CI 0.68-1.84; 28% mediated). Our results suggest that circulating free estradiol plays an important mediating role in the adiposity-breast cancer relationship but does not explain all of the association.
-
5.
The causal pathway effects of a physical activity intervention on adiposity in children: The KISS Study cluster randomized clinical trial.
Lima, RA, Andersen, LB, Soares, FC, Kriemler, S
Scandinavian journal of medicine & science in sports. 2020;(9):1685-1691
-
-
Free full text
-
Abstract
BACKGROUND Very little information on the potential mechanisms of the physical activity interventions effects on adiposity is available. We evaluated the possible mediating factors of a physical activity school-based intervention on the sum of skinfolds in children. METHODS This is a cluster randomized trial, secondary analysis of the KISS study. Children (n = 499) from the first and fifth grades were randomly assigned to intervention or control group. Adiposity was estimated by four skinfolds, aerobic fitness assessed by the shuttle run test, and insulin, triglycerides, total cholesterol, high-density lipoprotein (HDL), and glucose collected via fasting blood samples. RESULTS The intervention affected aerobic fitness (0.140 SD, 95% CI 0.011 to 0.270), triglycerides (0.217 SD, 95% CI -0.409 to -0.025), cholesterol/HDL ratio (-0.191 SD, 95% CI -0.334 to -0.047), glucose (-0.330 SD, 95% CI -0.538 to -0.121), and skinfolds (-0.122 SD, 95% CI -0.189 to -0.056). No intervention effect on insulin was found. We observed that changes in aerobic fitness impacted children's triglycerides and cholesterol/HDL ratio and consecutively the glucose levels mediating 30% of the intervention effect on skinfolds. CONCLUSIONS Our findings provided evidence of the positive metabolic distress caused by a physical activity intervention on adiposity levels in children.
-
6.
High-Risk Atherosclerosis and Metabolic Phenotype: The Roles of Ectopic Adiposity, Atherogenic Dyslipidemia, and Inflammation.
Lechner, K, McKenzie, AL, Kränkel, N, Von Schacky, C, Worm, N, Nixdorff, U, Lechner, B, Scherr, J, Weingärtner, O, Krauss, RM
Metabolic syndrome and related disorders. 2020;(4):176-185
-
-
Free full text
-
Abstract
Current algorithms for assessing risk of atherosclerotic cardiovascular disease (ASCVD) and, in particular, the reliance on low-density lipoprotein (LDL) cholesterol in conditions where this measurement is discordant with apoB and LDL-particle concentrations fail to identify a sizeable part of the population at high risk for adverse cardiovascular events. This results in missed opportunities for ASCVD prevention, most notably in those with metabolic syndrome, prediabetes, and diabetes. There is substantial evidence that accumulation of ectopic fat and associated metabolic traits are markers for and pathogenic components of high-risk atherosclerosis. Conceptually, the subset of advanced lesions in high-risk atherosclerosis that triggers vascular complications is closely related to a set of coordinated high-risk traits clustering around a distinct metabolic phenotype. A key feature of this phenotype is accumulation of ectopic fat, which, coupled with age-related muscle loss, creates a milieu conducive for the development of ASCVD atherogenic dyslipidemia, nonresolving inflammation, endothelial dysfunction, hyperinsulinemia, and impaired fibrinolysis. Sustained vascular inflammation, a hallmark of high-risk atherosclerosis, impairs plaque stabilization in this phenotype. This review describes how metabolic and inflammatory processes that are promoted in large measure by ectopic adiposity, as opposed to subcutaneous adipose tissue, relate to the pathogenesis of high-risk atherosclerosis. Clinical biomarkers indicative of these processes provide incremental information to standard risk factor algorithms and advanced lipid testing identifies atherogenic lipoprotein patterns that are below the discrimination level of standard lipid testing. This has the potential to enable improved identification of high-risk patients who are candidates for therapeutic interventions aimed at prevention of ASCVD.
-
7.
Empagliflozin Effectively Lowers Liver Fat Content in Well-Controlled Type 2 Diabetes: A Randomized, Double-Blind, Phase 4, Placebo-Controlled Trial.
Kahl, S, Gancheva, S, Straßburger, K, Herder, C, Machann, J, Katsuyama, H, Kabisch, S, Henkel, E, Kopf, S, Lagerpusch, M, et al
Diabetes care. 2020;(2):298-305
Abstract
OBJECTIVE To evaluate whether the sodium-glucose cotransporter 2 inhibitor empagliflozin (EMPA) reduces liver fat content (LFC) in recent-onset and metabolically well-controlled type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS Patients with T2D (n = 84) (HbA1c 6.6 ± 0.5% [49 ± 10 mmol/mol], known disease duration 39 ± 27 months) were randomly assigned to 24 weeks of treatment with 25 mg daily EMPA or placebo. The primary end point was the difference of the change in LFC as measured with magnetic resonance methods from 0 (baseline) to 24 weeks between groups. Tissue-specific insulin sensitivity (secondary outcome) was assessed by two-step clamps using an isotope dilution technique. Exploratory analysis comprised circulating surrogate markers of insulin sensitivity and liver function. Statistical comparison was done by ANCOVA adjusted for respective baseline values, age, sex, and BMI. RESULTS EMPA treatment resulted in a placebo-corrected absolute change of -1.8% (95% CI -3.4, -0.2; P = 0.02) and relative change in LFC of -22% (-36, -7; P = 0.009) from baseline to end of treatment, corresponding to a 2.3-fold greater reduction. Weight loss occurred only with EMPA (placebo-corrected change -2.5 kg [-3.7, -1.4]; P < 0.001), while no placebo-corrected change in tissue-specific insulin sensitivity was observed. EMPA treatment also led to placebo-corrected changes in uric acid (-74 mol/L [-108, -42]; P < 0.001) and high-molecular-weight adiponectin (36% [16, 60]; P < 0.001) levels from 0 to 24 weeks. CONCLUSIONS EMPA effectively reduces hepatic fat in patients with T2D with excellent glycemic control and short known disease duration. Interestingly, EMPA also decreases circulating uric acid and raises adiponectin levels despite unchanged insulin sensitivity. EMPA could therefore contribute to the early treatment of nonalcoholic fatty liver disease in T2D.
-
8.
Adiposity is related to neuroelectric indices of motor response preparation in preadolescent children.
Walk, AM, Raine, LB, Kramer, AF, Cohen, NJ, Hillman, CH, Khan, NA
International journal of psychophysiology : official journal of the International Organization of Psychophysiology. 2020;:176-183
Abstract
OBJECTIVE Event-related brain potentials (ERPs) have been utilized to study the cognitive implications of health-related behaviors, although many questions remain regarding the neural correlates underlying the cognition and adiposity relationship in childhood. Specifically, it is unknown whether excess fat mass is associated with the neural correlates of motor preparation and activation. The present work examined interrelationships between adiposity and ERPs that index inhibition, stimulus evaluation, and motor planning. METHOD To further elucidate the neural components of inhibitory control that are sensitive to adiposity, N2, P3, and response- and stimulus-locked Lateralized Readiness Potential (LRPs) were measured while preadolescent children completed an attentional inhibition task. Whole body percent adiposity was measured via dual-energy x-ray absorptiometry (DXA). RESULTS Adiposity was related to the response-locked LRP amplitudes and marginally to P3 amplitude during the incongruent trials, such that participants with less adiposity elicited larger LRP and P3 components. Furthermore, P3 was strongly related to participant reaction times, suggesting that while LRP is strongly associated with adiposity, P3 has a more direct relationship to behavioral task performance. CONCLUSIONS The results suggest that while different cognitive functions may be affected by health-related characteristics, stimulus evaluation and motor activation may be particularly sensitive to excess adiposity in children. These findings extend previous work implicating adiposity in cognitive health in the pediatric population. STUDY IMPORTANCE Clinical Registry Number: NCT02630667 at https://clinicaltrials.gov.
-
9.
Body size, silhouette trajectory and the risk of breast cancer in a Moroccan case-control study.
Khalis, M, Dossus, L, Rinaldi, S, Biessy, C, Moskal, A, Charaka, H, Fort, E, His, M, Mellas, N, Nejjari, C, et al
Breast cancer (Tokyo, Japan). 2020;(4):748-758
Abstract
BACKGROUND There is convincing evidence demonstrating that body size characteristics such as adiposity and height are associated with breast cancer in westernized countries. However, little is known about this relationship in North African countries currently undergoing nutritional transition and industrialization. The aim of this study was to explore associations between various body size characteristics, silhouette trajectories and the risk of breast cancer among Moroccan women. METHODS In this case-control study conducted in the Fez region (2016-2017), detailed measures of body size were collected for 300 cases of breast cancer and 300 matched controls. Unconditional logistic regression was used to assess the association between body size and breast cancer risk adjusting for confounding factors. RESULTS Higher waist circumference and hip circumference were positively associated with breast cancer risk in pre- (highest [T3] vs. lowest tertile [T1]: OR = 2.92, 95% confidence intervals [CI]: 1.33-6.42; OR = 3.00, 95% CI: 1.42-6.33, respectively) and post-menopausal women (T3 vs. T1: OR = 4.46, 95% CI: 1.86-10.66; OR = 4.08, 95% CI: 1.76-9.42, respectively). Body shape at younger ages (6-11 years) was inversely associated with the risk of breast cancer in premenopausal women (large vs. lean silhouette: OR = 0.31, 95% CI: 0.12-0.80). Women with the greatest increase in body shape trajectory had higher risk for both pre- and post-menopausal breast cancer (T3 vs. T1: OR = 2.74, 95% CI: 1.03-7.26; OR = 3.56, 95% CI: 1.34-9.44, respectively). CONCLUSION Our findings suggest that adiposity, body shape at younger ages, and silhouette trajectory may play a role in the development of pre- and post-menopausal breast cancer among Moroccan women. Larger-scale prospective studies are needed to confirm our findings and to explore these associations with breast cancer subtypes.
-
10.
Genetic Studies of Leptin Concentrations Implicate Leptin in the Regulation of Early Adiposity.
Yaghootkar, H, Zhang, Y, Spracklen, CN, Karaderi, T, Huang, LO, Bradfield, J, Schurmann, C, Fine, RS, Preuss, MH, Kutalik, Z, et al
Diabetes. 2020;(12):2806-2818
-
-
Free full text
-
Abstract
Leptin influences food intake by informing the brain about the status of body fat stores. Rare LEP mutations associated with congenital leptin deficiency cause severe early-onset obesity that can be mitigated by administering leptin. However, the role of genetic regulation of leptin in polygenic obesity remains poorly understood. We performed an exome-based analysis in up to 57,232 individuals of diverse ancestries to identify genetic variants that influence adiposity-adjusted leptin concentrations. We identify five novel variants, including four missense variants, in LEP, ZNF800, KLHL31, and ACTL9, and one intergenic variant near KLF14. The missense variant Val94Met (rs17151919) in LEP was common in individuals of African ancestry only, and its association with lower leptin concentrations was specific to this ancestry (P = 2 × 10-16, n = 3,901). Using in vitro analyses, we show that the Met94 allele decreases leptin secretion. We also show that the Met94 allele is associated with higher BMI in young African-ancestry children but not in adults, suggesting that leptin regulates early adiposity.