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Current opinion on dietary advice in order to preserve fat-free mass during a low-calorie diet.
Rondanelli, M, Faliva, MA, Gasparri, C, Peroni, G, Spadaccini, D, Maugeri, R, Nichetti, M, Infantino, V, Perna, S
Nutrition (Burbank, Los Angeles County, Calif.). 2020;:110667
Abstract
OBJECTIVES The loss of fat-free mass (FFM) that occurs during weight loss secondary to low-calorie diet can lead to numerous and deleterious consequences. We performed a review to evaluate the state of the art on metabolic and nutritional correlates of loss of fat free mass during low calorie diet and treatment for maintaining fat free mass. METHODS This review included 44 eligible studies. There are various diet strategies to maintain FFM during a low-calorie diet, including adoption of a very low carbohydrate ketogenic diet (VLCKD) and taking an adequate amount of specific nutrients (vitamin D, leucine, whey protein). RESULTS Regarding the numerous and various low-calorie diet proposals for achieving weight loss, the comparison of VLCKD with prudent low-calorie diet found that FFM was practically unaffected by VLCKD. There are numerous possible mechanisms for this, involving insulin and the insulin-like growth factor-1-growth hormone axis, which acts by stimulating protein synthesis. CONCLUSIONS Considering protein and amino acids intake, an adequate daily intake of leucine (4 g/d) and whey protein (20 g/d) is recommended. Regarding vitamin D, if the blood vitamin D has low values (<30 ng/mL), it is mandatory that adequate supplementation is provided, specifically calcifediol, because in the obese patient this form is recommended to avoid seizure in the adipose tissue; 3 to 4 drops/d or 20 to 30 drops/wk of calcifediol are generally adequate to restore normal 25(OH)D plasma levels in obese patients.
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Walking in the Light: How History of Physical Activity, Sunlight, and Vitamin D Account for Body Fat-A UK Biobank Study.
Klinedinst, BS, Meier, NF, Larsen, B, Wang, Y, Yu, S, Mochel, JP, Le, S, Wolf, T, Pollpeter, A, Pappas, C, et al
Obesity (Silver Spring, Md.). 2020;(8):1428-1437
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OBJECTIVE The high prevalence of vitamin D deficiency and obesity drives the need for successful strategies that elevate vitamin D levels, prevent adipogenesis, and stimulate lipolysis. This study provides a theoretical model to evaluate how physical activity (PA) and sunlight exposure influence serum vitamin D levels and regional adiposity. This study hypothesized a posteriori that sunlight is associated with undifferentiated visceral adiposity by increasing the ratio of brown to white adipose tissue. METHODS Using 10-year longitudinal data, accelerometry, a sun-exposure questionnaire, and regional adiposity quantified by dual-energy x-ray absorptiometry imaging, a structural-equation mediation model of growth curves was constructed with a data-driven methodology. RESULTS Sunlight and PA conjointly increased serum vitamin D. Changes in vitamin D levels partially mediated how sunlight and PA impacted adiposity in visceral and subcutaneous regions within a subjective PA model. In an objective PA model, vitamin D was a mediator for subcutaneous regions only. Interestingly, sunlight was associated with less adiposity in subcutaneous regions but greater adiposity in visceral regions. CONCLUSIONS Sunlight and PA may increase vitamin D levels. For the first time, this study characterizes a positive association between sunlight and visceral adiposity. Further investigation and experimentation are necessary to clarify the physiological role of sunlight exposure on adipose tissue.
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Free fatty acid processing diverges in human pathologic insulin resistance conditions.
Sekizkardes, H, Chung, ST, Chacko, S, Haymond, MW, Startzell, M, Walter, M, Walter, PJ, Lightbourne, M, Brown, RJ
The Journal of clinical investigation. 2020;(7):3592-3602
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BACKGROUNDPostreceptor insulin resistance (IR) is associated with hyperglycemia and hepatic steatosis. However, receptor-level IR (e.g., insulin receptor pathogenic variants, INSR) causes hyperglycemia without steatosis. We examined 4 pathologic conditions of IR in humans to examine pathways controlling lipid metabolism and gluconeogenesis.METHODSCross-sectional study of severe receptor IR (INSR, n = 7) versus postreceptor IR that was severe (lipodystrophy, n = 14), moderate (type 2 diabetes, n = 9), or mild (obesity, n = 8). Lipolysis (glycerol turnover), hepatic glucose production (HGP), gluconeogenesis (deuterium incorporation from body water into glucose), hepatic triglyceride (magnetic resonance spectroscopy), and hepatic fat oxidation (plasma β-hydroxybutyrate) were measured.RESULTSLipolysis was 2- to 3-fold higher in INSR versus all other groups, and HGP was 2-fold higher in INSR and lipodystrophy versus type 2 diabetes and obesity (P < 0.001), suggesting severe adipose and hepatic IR. INSR subjects had a higher contribution of gluconeogenesis to HGP, approximately 77%, versus 52% to 59% in other groups (P = 0.0001). Despite high lipolysis, INSR subjects had low hepatic triglycerides (0.5% [interquartile range 0.1%-0.5%]), in contrast to lipodystrophy (10.6% [interquartile range 2.8%-17.1%], P < 0.0001). β-hydroxybutyrate was 2- to 7-fold higher in INSR versus all other groups (P < 0.0001), consistent with higher hepatic fat oxidation.CONCLUSIONThese data support a key pathogenic role of adipose tissue IR to increase glycerol and FFA availability to the liver in both receptor and postreceptor IR. However, the fate of FFA diverges in these populations. In receptor-level IR, FFA oxidation drives gluconeogenesis rather than being reesterified to triglyceride. In contrast, in postreceptor IR, FFA contributes to both gluconeogenesis and hepatic steatosis.TRIAL REGISTRATIONClinicalTrials.gov NCT01778556, NCT00001987, and NCT02457897.FUNDINGNational Institute of Diabetes and Digestive and Kidney Diseases, US Department of Agriculture/Agricultural Research Service 58-3092-5-001.
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Seven-day overfeeding enhances adipose tissue dietary fatty acid storage and decreases myocardial and skeletal muscle dietary fatty acid partitioning in healthy subjects.
Noll, C, Montastier, É, Amrani, M, Kunach, M, Frisch, F, Fortin, M, Bouffard, L, Dubreuil, S, Phoenix, S, Cunnane, SC, et al
American journal of physiology. Endocrinology and metabolism. 2020;(2):E286-E296
Abstract
Increased myocardial partitioning of dietary fatty acids (DFA) and decreased left ventricular (LV) function is associated with insulin resistance in prediabetes. We hypothesized that enhanced myocardial DFA partitioning and reduced LV function might be induced concomitantly with reduced insulin sensitivity upon a 7-day hypercaloric (+50% in caloric intake), high-saturated fat (~11%energy), and simple carbohydrates (~54%energy) diet (HIGHCAL) versus an isocaloric diet (ISOCAL) with a moderate amount of saturated fat (~8%energy) and carbohydrates (~50%energy). Thirteen healthy subjects (7 men/6 women) underwent HIGHCAL versus ISOCAL in a randomized crossover design, with organ-specific DFA partitioning and LV function measured using the oral 14(R,S)-[18F]fluoro-6-thia-heptadecanoic acid and [11C]acetate positron emission tomography methods at the end of both interventions. HIGHCAL induced a decrease in insulin sensitivity indexes with no significant change in body composition. HIGHCAL led to increased subcutaneous abdominal (+4.2 ± 1.6%, P < 0.04) and thigh (+2.4 ± 1.2%, P < 0.08) adipose tissue storage and reduced cardiac (-0.31 ± 0.11 mean standard uptake value [(SUV), P < 0.03] and skeletal muscle (-0.17 ± 0.08 SUV, P < 0.05) DFA partitioning without change in LV function. We conclude that early increase in adipose tissue DFA storage protects the heart and skeletal muscles from potential deleterious effects of DFA.
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Platelet-rich plasma counteracts detrimental effect of high-glucose concentrations on mesenchymal stem cells from Bichat fat pad.
D'Esposito, V, Lecce, M, Marenzi, G, Cabaro, S, Ambrosio, MR, Sammartino, G, Misso, S, Migliaccio, T, Liguoro, P, Oriente, F, et al
Journal of tissue engineering and regenerative medicine. 2020;(5):701-713
Abstract
Diabetic patients display increased risk of periodontitis and failure in bone augmentation procedures. Mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP) represent a relevant advantage in tissue repair process and regenerative medicine. We isolated MSCs from Bichat's buccal fat pad (BFP) and measured the effects of glucose and PRP on cell number and osteogenic differentiation potential. Cells were cultured in the presence of 5.5-mM glucose (low glucose [LG]) or 25-mM glucose (high glucose [HG]). BFP-MSC number was significantly lower when cells were cultured in HG compared with those in LG. Following osteogenic differentiation procedures, calcium accumulation, alkaline phosphatase activity, and expression of osteogenic markers were significantly lower in HG compared with LG. Exposure of BFP-MSC to PRP significantly increased cell number and osteogenic differentiation potential, reaching comparable levels in LG and in HG. Thus, high-glucose concentrations impair BFP-MSC growth and osteogenic differentiation. However, these detrimental effects are largely counteracted by PRP.
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Dietary Regulation of Immunity.
Lee, AH, Dixit, VD
Immunity. 2020;(3):510-523
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Integrated immunometabolic responses link dietary intake, energy utilization, and storage to immune regulation of tissue function and is therefore essential for the maintenance and restoration of homeostasis. Adipose-resident leukocytes have non-traditional immunological functions that regulate organismal metabolism by controlling insulin action, lipolysis, and mitochondrial respiration to control the usage of substrates for production of heat versus ATP. Energetically expensive vital functions such as immunological responses might have thus evolved to respond accordingly to dietary surplus and deficit of macronutrient intake. Here, we review the interaction of dietary intake of macronutrients and their metabolism with the immune system. We discuss immunometabolic checkpoints that promote healthspan and highlight how dietary fate and regulation of glucose, fat, and protein metabolism might affect immunity.
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B-vitamins and body composition: integrating observational and experimental evidence from the B-PROOF study.
Oliai Araghi, S, Braun, KVE, van der Velde, N, van Dijk, SC, van Schoor, NM, Zillikens, MC, de Groot, LCPGM, Uitterlinden, AG, Stricker, BH, Voortman, T, et al
European journal of nutrition. 2020;(3):1253-1262
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PURPOSE Higher folate and vitamin-B12 have been linked to lower risk of overweight. However, whether this is a causal effect of these B-vitamins on obesity risk remains unclear and evidence in older individuals is scarce. This study aimed to assess the role of B-vitamin supplementation and levels on body composition in older individuals. METHODS A double-blind, randomized controlled trial in 2919 participants aged ≥ 65 years with elevated homocysteine levels. The intervention comprised a 2-year supplementation with a combination of folic acid (400 µg) and vitamin B12 (500 µg), or with placebo. Serum folate, vitamin-B12, active vitamin-B12 (HoloTC), methylmalonic acid (MMA), and anthropometrics were measured at baseline and after 2 years of follow-up. Dietary intake of folate and vitamin-B12 was measured at baseline in a subsample (n = 603) using a validated food-frequency questionnaire. Fat mass index (FMI) and fat-free mass index (FFMI) were assessed with Dual Energy X-ray absorptiometry (DXA). RESULTS Cross-sectional analyses showed that a 1 nmol/L higher serum folate was associated with a 0.021 kg/m2 lower BMI (95% CI - 0.039; - 0.004). Higher HoloTC (per pmol/L log-transformed) was associated with a 0.955 kg/m2 higher FMI (95% CI 0.262; 1.647), and higher MMA (per μgmol/L) was associated with a 1.108 kg/m2 lower FMI (95% CI - 1.899; - 0.316). However, random allocation of B-vitamins did not have a significant effect on changes in BMI, FMI or FFMI during 2 years of intervention. CONCLUSIONS Although observational data suggested that folate and vitamin B12 status are associated with body composition, random allocation of a supplement with both B-vitamins combined versus placebo did not confirm an effect on BMI or body composition.
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Machine learning to predict the long-term risk of myocardial infarction and cardiac death based on clinical risk, coronary calcium, and epicardial adipose tissue: a prospective study.
Commandeur, F, Slomka, PJ, Goeller, M, Chen, X, Cadet, S, Razipour, A, McElhinney, P, Gransar, H, Cantu, S, Miller, RJH, et al
Cardiovascular research. 2020;(14):2216-2225
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AIMS: Our aim was to evaluate the performance of machine learning (ML), integrating clinical parameters with coronary artery calcium (CAC), and automated epicardial adipose tissue (EAT) quantification, for the prediction of long-term risk of myocardial infarction (MI) and cardiac death in asymptomatic subjects. METHODS AND RESULTS Our study included 1912 asymptomatic subjects [1117 (58.4%) male, age: 55.8 ± 9.1 years] from the prospective EISNER trial with long-term follow-up after CAC scoring. EAT volume and density were quantified using a fully automated deep learning method. ML extreme gradient boosting was trained using clinical co-variates, plasma lipid panel measurements, risk factors, CAC, aortic calcium, and automated EAT measures, and validated using repeated 10-fold cross validation. During mean follow-up of 14.5 ± 2 years, 76 events of MI and/or cardiac death occurred. ML obtained a significantly higher AUC than atherosclerotic cardiovascular disease (ASCVD) risk and CAC score for predicting events (ML: 0.82; ASCVD 0.77; CAC: 0.77, P < 0.05 for all). Subjects with a higher ML score (by Youden's index) had high hazard of suffering events (HR: 10.38, P < 0.001); the relationships persisted in multivariable analysis including ASCVD-risk and CAC measures (HR: 2.94, P = 0.005). Age, ASCVD-risk, and CAC were prognostically important for both genders. Systolic blood pressure was more important than cholesterol in women, and the opposite in men. CONCLUSIONS In this prospective study, machine learning used to integrate clinical and quantitative imaging-based variables significantly improves prediction of MI and cardiac death compared with standard clinical risk assessment. Following further validation, such a personalized paradigm could potentially be used to improve cardiovascular risk assessment.
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Effect of exercise training on insulin sensitivity, hyperinsulinemia and ectopic fat in black South African women: a randomized controlled trial.
Fortuin-de Smidt, MC, Mendham, AE, Hauksson, J, Hakim, O, Stefanovski, D, Clamp, L, Phiri, L, Swart, J, Goff, LM, Micklesfield, LK, et al
European journal of endocrinology. 2020;(1):51-61
Abstract
OBJECTIVE We investigated the effects of a 12-week exercise intervention on insulin sensitivity (SI) and hyperinsulinemia and associated changes in regional and ectopic fat. RESEARCH DESIGN AND METHODS Healthy, black South African women with obesity (mean age 23 ± 3.5 years) and of isiXhosa ancestry were randomised into a 12-week aerobic and resistance exercise training group (n = 23) and a no exercise group (control, n = 22). Pre and post-intervention testing included assessment of SI, insulin response to glucose (AIRg), insulin secretion rate (ISR), hepatic insulin extraction (FEL) and disposition index (DI) (AIRg × SI) (frequently sampled i.v. glucose tolerance test); fat mass and regional adiposity (dual-energy X-ray absorptiometry); hepatic, pancreatic and skeletal muscle fat content and abdominal s.c. and visceral adipose tissue volumes (MRI). RESULTS Exercise training increased VO2peak (mean ± s.d.: 24.9 ± 2.42 to 27.6 ± 3.39 mL/kg/min, P < 0.001), SI (2.0 (1.2-2.8) to 2.2 (1.5-3.7) (mU/l)-1 min-1, P = 0.005) and DI (median (interquartile range): 6.1 (3.6-7.1) to 6.5 (5.6-9.2) × 103 arbitrary units, P = 0.028), and decreased gynoid fat mass (18.5 ± 1.7 to 18.2 ± 1.6%, P < 0.001) and body weight (84.1 ± 8.7 to 83.3 ± .9.7 kg, P = 0.038). None of these changes were observed in the control group, but body weight increased (P = 0.030). AIRg, ISR and FEL, VAT, SAT and ectopic fat were unaltered after exercise training. The increase in SI and DI were not associated with changes in regional or ectopic fat. CONCLUSION Exercise training increased SI independent from changes in hyperinsulinemia and ectopic fat, suggesting that ectopic fat might not be a principal determinant of insulin resistance in this cohort.
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Perimenopause, body fat, metabolism and menopausal symptoms in relation to serum markers of adiposity, inflammation and digestive metabolism.
Palla, G, Ramírez-Morán, C, Montt-Guevara, MM, Salazar-Pousada, D, Shortrede, J, Simoncini, T, Grijalva-Grijalva, I, Pérez-López, FR, Chedraui, P
Journal of endocrinological investigation. 2020;(6):809-820
Abstract
BACKGROUND Perimenopausal women gain weight that may alter inflammatory status, endocrine equilibrium, and the intensity of vasomotor symptoms. OBJECTIVE To measure serum levels of markers related to adiposity, inflammation/angiogenesis and digestive metabolism and correlate them with body mass index (BMI), waist-to-hip ratio (WHR), metabolic parameters and menopausal symptoms (assessed with the 10-item Cervantes Scale [CS-10]). METHODS Serum of perimenopausal women (n = 24), STRAW stages-2 and -1, was analyzed using the Bio-Plex 200 System technology to assess 30 proposed analytes. The MetS was defined by the American Heart Association criteria and women were divided as: normal BMI (NBMI), excessive BMI (EBMI), and EBMI with MetS (EBMI-MetS). RESULTS Weight, BMI, abdominal circumference, WHR, systolic blood pressure, glucose and triglyceride levels were significantly higher and high-density lipoprotein cholesterol (HDL-C) was lower in EBMI-MetS women compared to NBMI ones. Insulin, C-peptide, resistin, adipsin, GIP, leptin, IL-6, FGF21 and PAI-1 levels were significantly higher and ghrelin and IGFBP-1 lower in EBMI-MetS women as compared to NBMI ones. Spearman's correlation of pooled data showed a significant positive correlation between abdominal perimeter and WHR and C-peptide, insulin, adipsin, resistin, leptin, PAI-1 and FGF21 and a negative correlation with IGFBP-1 levels. Total CS-10 scores and hot flush intensity did not differ between studied groups, yet positively correlated with anthropometric values but not with studied analytes. CONCLUSION Perimenopausal women with EBMI and the MetS showed an altered metabolic profile, but no differences in menopausal symptoms which also did not correlate with changes in studied biomarkers.