Caloric Restriction-induced Weight Loss Research Articles

Gut microbiota promoting propionic acid production accompanies caloric restriction-induced intentional weight loss in cats

Rodent models and human clinical studies have shown gut microbiota-derived short-chain fatty acids (SCFAs) play roles in obesity and insulin resistance. These roles have been minimally explored in cats, where in the USA an estimated 60% of cats are overweight or obese. Overweight/obese research cats (n = 7) were transitioned from a maintenance diet to a reduced calorie diet fed ad libitum for 7 days, then calories were restricted to achieve 1–2% weight loss per week for an additional 77 days. Cats then received their original maintenance diet again for 14 days. Significant intentional weight loss was noted after calorie restriction (adjusted p < 0.0001). 16S rRNA gene amplicon sequencing and targeted SCFA metabolomics were performed on fecal samples. Fecal microbial community structure significantly differed between the four study phases (PERMANOVA p = 0.011). Fecal propionic acid was significantly higher during caloric restriction-induced weight loss (adjusted p < 0.05). Repeated measures correlation revealed the relative abundances of Prevotella 9 copri (correlation coefficient = 0.532, 95% CI (0.275, 0.717), p = 0.0002) significantly correlated with propionic acid composition. Like humans, obese cats experienced an altered microbial community structure and function, favoring propionic acid production, during caloric restriction-induced weight loss.

The Impact of Interventional Weight Loss on Bone Marrow Adipose Tissue in People Living with Obesity and Its Connection to Bone Metabolism.

This review focuses on providing physicians with insights into the complex relationship between bone marrow adipose tissue (BMAT) and bone health, in the context of weight loss through caloric restriction or metabolic and bariatric surgery (MBS), in people living with obesity (PwO). We summarize the complex relationship between BMAT and bone health, provide an overview of noninvasive imaging techniques to quantify human BMAT, and discuss clinical studies measuring BMAT in PwO before and after weight loss. The relationship between BMAT and bone is subject to variations based on factors such as age, sex, menopausal status, skeletal sites, nutritional status, and metabolic conditions. The Bone Marrow Adiposity Society (BMAS) recommends standardizing imaging protocols to increase comparability across studies and sites, they have identified both water-fat imaging (WFI) and spectroscopy (1H-MRS) as accepted standards for in vivo quantification of BMAT. Clinical studies measuring BMAT in PwO are limited and have shown contradictory results. However, BMAT tends to be higher in patients with the highest visceral adiposity, and inverse associations between BMAT and bone mineral density (BMD) have been consistently found in PwO. Furthermore, BMAT levels tend to decrease after caloric restriction-induced weight loss. Although weight loss was associated with overall fat loss, a reduction in BMAT did not always follow the changes in fat volume in other tissues. The effects of MBS on BMAT are not consistent among the studies, which is at least partly related to the differences in the study population, skeletal site, and duration of the follow-up. Overall, gastric bypass appears to decrease BMAT, particularly in patients with diabetes and postmenopausal women, whereas sleeve gastrectomy appears to increase BMAT. More research is necessary to evaluate changes in BMAT and its connection to bone metabolism, either in PwO or in cases of weight loss through caloric restriction or MBS, to better understand the role of BMAT in this context and determine the local or systemic factors involved.

Proportion of caloric restriction-induced weight loss as skeletal muscle.

This study's objective was to develop models predicting the relative reduction in skeletal muscle (SM) mass during periods of voluntary calorie restriction (CR) and to validate model predictions in longitudinally monitored samples. The model development group included healthy nonexercising adults (n = 897) who had whole-body SM mass measured with magnetic resonance imaging. Model predictions of relative SM changes with CR were evaluated in two longitudinal studies, one 12 to 14 weeks in duration (n = 74) and the other 12 months in duration (n = 26). A series of SM prediction models were developed in a sample of 415 males and 482 females. Model-predicted changes in SM mass relative to changes in body weight (i.e., ΔSM/Δbody weight) with a representative model were (mean ± SE) 0.26 ± 0.013 in males and 0.14 ± 0.007 in females (sex difference, p < 0.001). The actual mean proportions of weight loss as SM in the longitudinal studies were 0.23 ± 0.02/0.20 ± 0.06 in males and 0.10 ± 0.02/0.17 ± 0.03 in females, similar to model-predicted values. Nonelderly males and females with overweight and obesity experience respective reductions in SM mass with voluntary CR in the absence of a structured exercise program of about 2 to 2.5 kg and 1 to 1.5 kg per 10-kg weight loss, respectively. These estimates are predicted to be influenced by interactions between age and body mass index in males, a hypothesis that needs future testing.

Network Analyses Reveal Negative Link Between Changes in Adipose Tissue GDF15 and BMI During Dietary-induced Weight Loss.

Adipose tissue (AT) transcriptome studies provide holistic pictures of adaptation to weight and related bioclinical settings changes. To implement AT gene expression profiling and investigate the link between changes in bioclinical parameters and AT gene expression during 3 steps of a 2-phase dietary intervention (DI). AT transcriptome profiling was obtained from sequencing 1051 samples, corresponding to 556 distinct individuals enrolled in a weight loss intervention (8-week low-calorie diet (LCD) at 800 kcal/day) followed with a 6-month ad libitum randomized DI. Transcriptome profiles obtained with QuantSeq sequencing were benchmarked against Illumina RNAseq. Reverse transcription quantitative polymerase chain reaction was used to further confirm associations. Cell specificity was assessed using freshly isolated cells and THP-1 cell line. During LCD, 5 modules were found, of which 3 included at least 1 bioclinical variable. Change in body mass index (BMI) connected with changes in mRNA level of genes with inflammatory response signature. In this module, change in BMI was negatively associated with changes in expression of genes encoding secreted protein (GDF15, CCL3, and SPP1). Through all phases of the DI, change in GDF15 was connected to changes in SPP1, CCL3, LIPA and CD68. Further characterization showed that these genes were specific to macrophages (with LIPA, CD68 and GDF15 expressed in anti-inflammatory macrophages) and GDF15 also expressed in preadipocytes. Network analyses identified a novel AT feature with GDF15 upregulated with calorie restriction induced weight loss, concomitantly to macrophage markers. In AT, GDF15 was expressed in preadipocytes and macrophages where it was a hallmark of anti-inflammatory cells.

Weight Loss and Exercise Differentially Affect Insulin Sensitivity, Body Composition, Cardiorespiratory Fitness, and Muscle Strength in Older Adults With Obesity: A Randomized Controlled Trial.

Aging-related disease risk is exacerbated by obesity and physical inactivity. It is unclear how weight loss and increased activity improve risk in older adults. We aimed to determine the effects of diet-induced weight loss with and without exercise on insulin sensitivity, VO2peak, body composition, and physical function in older obese adults. Physically inactive older (68.6 ± 4.5 years) obese (body mass index 37.4 ± 4.9 kg/m2) adults were randomized to health education control (HEC; n = 25); diet-induced weight loss (WL; n = 31); or weight loss and exercise (WLEX; n = 28) for 6 months. Insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp, body composition by dual-energy X-ray absorptiometry and MRI, strength by isokinetic dynamometry, and VO2peak by graded exercise test. WLEX improved (p < .05) peripheral insulin sensitivity (+75 ± 103%) versus HEC (+12 ± 67%); WL (+36 ± 47%) versus HEC did not reach statistical significance. WLEX increased VO2peak (+7 ± 12%) versus WL (-2 ± 24%) and prevented reductions in strength and lean mass induced by WL (p < .05). WLEX decreased abdominal adipose tissue (-16 ± 9%) versus HEC (-3 ± 8%) and intermuscular adipose tissue (-15 ± 13%) versus both HEC (+9 ± 15%) and WL (+2 ± 11%; p < .01). Exercise with weight loss improved insulin sensitivity and VO2peak, decreased ectopic fat, and preserved lean mass and strength. Weight loss alone decreased lean mass and strength. Older adults intending to lose weight should perform regular exercise to promote cardiometabolic and functional benefits, which may not occur with calorie restriction-induced weight loss alone.

Carbohydrates to Prevent and Treat Obesity in a Murine Model of Diet-Induced Obesity

Introduction: The biggest risk factor for obesity and its associated comorbidities is a Western diet. This Western diet induces adipose tissue (AT) inflammation, which causes an AT dysfunction. Since AT is a vital endocrine organ, its dysfunction damages other organs, thus inducing a state of chronic inflammation and causing various comorbidities. Even though it is evident a Western diet, high in fat and carbohydrates, induces obesity and its complications, it is not known yet which macronutrient plays the most important role. Therefore, the aim of this study was to investigate the effect of macronutrient composition on obesity and to reverse the Western diet-induced metabolic risk via caloric restriction (CR) or a change of diet composition. Materials and Methods: Male, C57BL/6JRj mice were fed with a diet high in fat, sucrose, fructose, sucrose and fructose, starch, a Western diet, or a control diet for 15 weeks. To assess reversibility of the metabolic risk, mice were first made obese via 15 weeks of WD and then put on either a CR or switched to a sucrose-rich diet. Results: A sucrose-rich and high-starch diet induced less obesity and a better metabolic profile than a Western diet, evidenced by less hepatic steatosis, lower plasma cholesterol, and less insulin resistance. Furthermore, these diets induced less intra-abdominal AT inflammation than a Western diet, since mRNA levels of pro-inflammatory markers were lower and there was less macrophage infiltration. Expression of tight junction markers in colon tissue was higher in the sucrose-rich and high-starch group than the Western group, indicating a better intestinal integrity upon sucrose-rich and high-starch feeding. Additionally, CR induced weight loss and decreased both metabolic abnormalities and AT inflammation, regardless of macronutrient composition. However, effects were more pronounced upon CR with sucrose-rich or high-starch diet. Even without CR, switching obese mice to a sucrose-rich diet induced weight loss and decreased AT inflammation and metabolic aberrations. Discussion: A diet high in sucrose or starch induces less obesity and obesity-associated complications. Moreover, switching obese mice to a sucrose-rich diet elicits weight loss and decreases obesity-induced metabolic complications, highlighting the potential of carbohydrates to treat obesity.

Roux-en-Y gastric bypass surgery in Zucker rats induces bacterial and systemic metabolic changes independent of caloric restriction-induced weight loss

ABSTRACT Mechanisms of Roux-en-Y gastric bypass (RYGB) surgery are not fully understood. This study aimed to investigate weight loss-independent bacterial and metabolic changes, as well as the absorption of bacterial metabolites and bile acids through the hepatic portal system following RYGB surgery. Three groups of obese Zucker (fa/fa) rats were included: RYGB (n = 11), sham surgery and body weight matched with RYGB (Sham-BWM, n = 5), and sham surgery fed ad libitum (Sham-obese, n = 5). Urine and feces were collected at multiple time points, with portal vein and peripheral blood obtained at the end of the study. Metabolic phenotyping approaches and 16S rRNA gene sequencing were used to determine the biochemical and bacterial composition of the samples, respectively. RYGB surgery-induced distinct metabolic and bacterial disturbances, which were independent of weight loss through caloric restriction. RYGB resulted in lower absorption of phenylalanine and choline, and higher urinary concentrations of host-bacterial co-metabolites (e.g., phenylacetylglycine, indoxyl sulfate), together with higher fecal trimethylamine, suggesting enhanced bacterial aromatic amino acid and choline metabolism. Short chain fatty acids (SCFAs) were lower in feces and portal vein blood from RYGB group compared to Sham-BWM, accompanied with lower abundances of Lactobacillaceae, and Ruminococcaceae known to contain SCFA producers, indicating reduced bacterial fiber fermentation. Fecal γ-amino butyric acid (GABA) was found in higher concentrations in RYGB than that in Sham groups and could play a role in the metabolic benefits associated with RYGB surgery. While no significant difference in urinary BA excretion, RYGB lowered both portal vein and circulating BA compared to Sham groups. These findings provide a valuable resource for how dynamic, multi-systems changes impact on overall metabolic health, and may provide potential therapeutic targets for developing downstream non-surgical treatment for metabolic disease.

Caloric restriction-induced weight loss with a high-fat diet does not fully recover visceral adipose tissue inflammation in previously obese C57BL/6 mice.

Caloric restriction (CR) reduces body weight and systemic inflammation, but the effects on adipose tissue under dietary lipid overload are controversial. We evaluated the effects of CR-induced weight loss with a high-fat diet on adipose tissue inflammation of obese mice. Male mice were assigned into low-fat diet (LF) and high-fat diet (HF) groups. After 8 weeks, the mice in the HF group were reassigned for another 7 weeks into the following 3 conditions: (i) kept in the HF condition; (ii) changed to low-fat diet ad libitum (LFAL); and (iii) changed to high-fat calorie-restricted (RHF) diet to reach LFAL body weight. Serum markers, adipocytokines, morphology, and inflammatory infiltrates in retroperitoneal adipose tissue (RAT) were accessed. The body weights of the LFAL and RHF groups were reduced, equaling the body weights of the LF group. The LFAL mice had restored almost all inflammatory markers as the LF mice, except tumor necrosis factor-alpha (TNF-α), monocyte chemoattractant protein-1 (MCP-1), and adiponectin. Compared with the HF group, the RHF group had lowered visceral adiposity, retroperitoneal adipocyte sizes, and RAT inflammatory cell infiltration, as well as TNF-α, interleukin-6, and hepatic and serum C-reactive protein, which were higher than that of the LFAL group; adiponectin and MCP-1 did not change. CR with high-fat diet reduced body weight and attenuated visceral adiposity but did not fully recover visceral tissue inflammation. Novelty Caloric restriction in a high-fat diet ameliorated visceral adiposity. Caloric restriction in a high-fat diet did not recover visceral adipose tissue inflammation.

Apolipoprotein M: a novel adipokine decreasing with obesity and upregulated by calorie restriction

The adipose tissue (AT) is a secretory organ producing a wide variety of factors that participate in the genesis of metabolic disorders linked to excess fat mass. Weight loss improves obesity-related disorders. Transcriptomic studies on human AT, and a combination of analyses of transcriptome and proteome profiling of conditioned media from adipocytes and stromal cells isolated from human AT, have led to the identification of apolipoprotein M (apoM) as a putative adipokine. We aimed to validate apoM as novel adipokine, investigate the relation of AT APOM expression with metabolic syndrome and insulin sensitivity, and study the regulation of its expression in AT and secretion during calorie restriction-induced weight loss. We examined APOM mRNA level and secretion in AT from 485 individuals enrolled in 5 independent clinical trials, and in vitro in human multipotentadipose-derived stem cell adipocytes. APOM expression and secretion were measured during dieting. APOM was expressed in human subcutaneous and visceral AT, mainly by adipocytes. ApoM was released into circulation from AT, and plasma apoM concentrations correlate with AT APOM mRNA levels. In AT, APOM expression inversely correlated with adipocyte size, was lower in obese compared to lean individuals, and reduced in subjects with metabolic syndrome and type 2 diabetes. Regardless of fat depot, there was a positive relation between AT APOM expression and systemic insulin sensitivity, independently of fat mass and plasma HDL cholesterol. In human multipotentadipose-derived stem cell adipocytes, APOM expression was enhanced by insulin-sensitizing peroxisome proliferator-activated receptor agonists and inhibited by tumor necrosis factor α, a cytokine that causes insulin resistance. In obese individuals, calorie restriction increased AT APOM expression and secretion. ApoM is a novel adipokine, the expression of which is a hallmark of healthy AT and is upregulated by calorie restriction. AT apoM deserves further investigation as a potential biomarker of risk for diabetes and cardiovascular diseases.

Effects of Obesity and Gastric Bypass Surgery on Nutrient Sensors, Endocrine Cells, and Mucosal Innervation of the Mouse Colon.

Background: Nutrient-sensing receptors located on enteroendocrine (EEC) cells modulate appetite via detection of luminal contents. Colonic ‘tasting’ of luminal contents may influence changes to appetite observed in obesity and after weight loss induced by bariatric surgery. We assessed the effects of obesity and gastric bypass-induced weight loss on expression of nutrient-sensing G-protein coupled receptors (GPCRs), EEC and enterochromaffin (EC) cells and mucosal innervation. Methods: qPCR and immunohistochemistry were used to study colonic tissue from (a) chow-fed/lean, (b) high-fat fed/obese, (c) Roux-en-Y gastric bypass surgery (RYGB), and (d) calorie restriction-induced weight loss mice. Results: Expression of GPR41, GPR43, GPR40, GPR120, GPR84, GPR119, GPR93 and T1R3 was increased in obese mice. Obesity-induced overexpression of GPR41, 40, 84, and 119 further increased after RYGB whereas GPR120 and T1R3 decreased. RYGB increased TGR5 expression. L-cells, but not EC cells, were increased after RYGB. No differences in mucosal innervation by protein gene product (PGP) 9.5 and GLP-1R-positive nerve fibers were observed. Stimulation of colonic mucosa with GPR41, GPR40, GPR85, GPR119, and TGR5 agonists increased cell activation marker expression. Conclusions: Several nutrient-sensing receptors induced activation of colonic EEC. Profound adaptive changes to the expression of these receptors occur in response to diet and weight loss induced by RYGB or calorie restriction.

Exercise Is Required to Improve Mitochondrial Respiratory Capacity in Skeletal Muscle of Older Obese Subjects during Calorie Restriction–Induced Weight Loss to Improve Insulin Sensitivity

Calorie restriction has been shown to have “anti-aging” effects in animal models, and calorie restriction-induced weight loss (CRWL) and exercise can both improve insulin sensitivity. The aim of this study was to investigate the effect of 6-month diet-induced weight loss intervention with or without the addition of exercise training on skeletal muscle mitochondrial respiratory capacity and IS. Methods: Forty-four older adults with obesity were randomized to one of the following 6-month intervention: Health education (CON: n=14, age=70±4 years, BMI=34±5kg/m2), Diet induced weight-loss (DIWL: n=14, age=70±4 years, BMI=36±5kg kg/m2), or Weight-loss and exercise (WLEX: n=16, age=66±3 years, BMI=37±5kg/m2). CRWL and WLEX participants had a goal of 10% weight-loss through calorie restriction. Subjects in the WLEX group completed a supervised exercise program. Mitochondrial respiratory capacity of permeabilized myofibers from biopsies was evaluated by high-resolution respirometry. Complex I+II supported maximal oxidative phosphorylation (OXPHOS), and maximal uncoupled respiration were evaluated. IS was determined by hyperinsulinemic euglycemic clamps. Results: IS improved in both CRWL (10.4%) and WLEX (50%) compared to CON (0.7%). However, while mitochondrial respiration was unchanged in the CON and CRWL groups after the 6-month intervention (p&amp;gt;0.05), subjects in the WLEX group presented an increased maximal OXPHOS (PRE: 50.7±10.1 vs. POST: 72.6±17.9 pmol/s*mg) and uncoupled respiration (PRE: 57.2±10.5 vs. POST: 79.6±19.3 pmol/s*mg) after the exercise training. Conclusions: Despite weight loss and exercise both improving insulin sensitivity, exercise is required to improve mitochondrial respiratory capacity in skeletal muscle of older obese human subjects undergoing calorie restriction-induced weight loss. Disclosure G. Distefano: None. R. Standley: None. E.A. Carnero: None. P.M. Coen: None. R.B. Vega: None. B.H. Goodpaster: None.

Significant improvement in cardiometabolic health in healthy nonobese individuals during caloric restriction-induced weight loss and weight loss maintenance.

Calorie restriction (CR) triggers benefits for healthspan including decreased risk of cardiometabolic disease (CVD). In an ancillary study to CALERIE 2, a 24-mo 25% CR study, we assessed the cardiometabolic effects of CR in 53 healthy, nonobese (BMI: 22-28 kg/m2) men ( n = 17) and women ( n = 36). The aim of this study was to investigate whether CR can reduce risk factors for CVD and insulin resistance in nonobese humans and, moreover, to assess whether improvements are exclusive to a period of weight loss or continue during weight maintenance. According to the energy balance method, the 25% CR intervention ( n = 34) produced 16.5 ± 1.5% (mean ± SE) and 14.8 ± 1.5% CR after 12 and 24 mo (M12, M24), resulting in significant weight loss (M12 -9 ± 0.5 kg, M24 -9 ± 0.5 kg, P < 0.001). Weight was maintained in the group that continued their habitual diet ad libitum (AL, n = 19). In comparison to AL, 24 mo of CR decreased visceral (-0.5 ± 0.01 kg, P < 0.0001) and subcutaneous abdominal adipose tissue (-1.9 ± 0.2kg, P < 0.001) as well as intramyocellular lipid content (-0.11 ± 0.05%, P = 0.031). Furthermore, CR decreased blood pressure (SBP -8 ± 3 mmHg, P = 0.005; DBP -6 ± 2 mmHg, P < 0.001), total cholesterol (-13.6 ± 5.3 mg/dl, P = 0.001), and LDL-cholesterol (-12.9 ± 4.4 mg/dl, P = 0.005), and the 10-yr risk of CVD-disease was reduced by 30%. Homeostasis model assessment of insulin resistance (HOMA-IR) decreased during weight loss in the CR group (-0.46 ± 0.15, P = 0.003), but this decrease was not maintained during weight maintenance (-0.11 ± 0.15, P = 0.458). In conclusion, sustained CR in healthy, nonobese individuals is beneficial in improving risk factors for cardiovascular and metabolic disease such as visceral adipose tissue mass, ectopic lipid accumulation, blood pressure, and lipid profile, whereas improvements in insulin sensitivity were only transient.

Calorie Restriction-induced Weight Loss and Exercise Have Differential Effects on Skeletal Muscle Mitochondria Despite Similar Effects on Insulin Sensitivity.

Skeletal muscle insulin resistance and reduced mitochondrial capacity have both been reported to be affected by aging. The purpose of this study was to compare the effects of calorie restriction-induced weight loss and exercise on insulin resistance, skeletal muscle mitochondrial content, and mitochondrial enzyme activities in older overweight to obese individuals. Insulin-stimulated rates of glucose disposal (Rd) were determined using the hyperinsulinemic euglycemic clamp before and after completing 16 weeks of either calorie restriction to induce weight loss (N = 7) or moderate exercise (N = 10). Mitochondrial volume density, mitochondria membrane content (cardiolipin), and activities of electron transport chain (rotenone-sensitive NADH-oxidase), tricarboxylic acid (TCA) cycle (citrate synthase) and β-oxidation pathway (β-hydroxyacyl CoA dehydrogenase; β-HAD) were measured in percutaneous biopsies of the vastus lateralis before and after the interventions. Rd improved similarly (18.2% ± 9.0%, p < .04) with both weight loss and exercise. Moderate exercise significantly increased mitochondrial volume density (14.5% ± 2.0%, p < .05), cardiolipin content (22.5% ± 13.4%, p < .05), rotenone-sensitive NADH-oxidase (65.7% ± 13.2%, p = .02) and β-HAD (30.7% ± 6.8%, p ≤ .03) activity, but not citrate synthase activity (10.1% ± 4.0%). In contrast, calorie restriction-induced weight loss did not affect mitochondrial content, NADH-oxidase or β-HAD, yet increased citrate synthase activity (44.1% ± 21.1%, p ≤ .04). Exercise (increase) or weight loss (decrease) induced a remodeling of cardiolipin with a small (2%-3%), but significant change in the relative content of tetralinoleoyl cardiolipin. Exercise increases both mitochondria content and mitochondrial electron transport chain and fatty acid oxidation enzyme activities within skeletal muscle, while calorie restriction-induced weight loss did not, despite similar improvements in insulin sensitivity in overweight older adults.

Cognitive Effects of Intentional Weight Loss in Elderly Obese Individuals With Mild Cognitive Impairment.

Obesity in midlife is a risk factor for dementia, but it is unknown if caloric restriction-induced weight loss could prevent cognitive decline and therefore dementia in elderly patients with cognitive impairment. To evaluate the cognitive effect of intentional weight loss in obese elderly patients with mild cognitive impairment (MCI), considering the influence of age, apolipoprotein E (APOE) genotype, physical activity, biochemical markers, and diet. Single-center, prospective controlled trial. Academic medical center. Eighty obese patients with MCI, aged 60 or older (68.1 ± 4.9 y, body mass index [BMI] 35.5 ± 4.4 kg/m(2), 83.7% women, 26.3% APOE allele ϵ4 carriers). Random allocation to conventional medical care alone (n = 40) or together with nutritional counselling (n = 40) in group meetings aiming to promote weight loss through caloric restriction for 12 months. clinical data, body composition, neuropsychological tests (main outcome), serum biomarkers, APOE genotype, physical performance, dietary recalls. Seventy-five patients completed the follow-up. BMI, on average, decreased 1.7 ± 1.8 kg/m(2) (P = .021), and most of the cognitive tests improved, without difference between the groups. In analysis with linear generalized models, the BMI decrease was associated with improvements in verbal memory, verbal fluency, executive function, and global cognition, after adjustment for education, gender, physical activity, and baseline tests. This association was strongest in younger seniors (for memory and fluency) and in APOE allele ϵ4 carriers (for executive function). Changes in homeostasis model assessment-estimated insulin resistance, C-reactive protein, leptin and intake of energy, carbohydrates, and fats were associated with improvement in cognitive tests. Intentional weight loss through diet was associated with cognitive improvement in patients with MCI.

Changes in glucose disposal after a caloric restriction-induced weight loss program in obese postmenopausal women: characteristics of positive and negative responders in a Montreal-Ottawa New Emerging Team study.

This study aims to investigate individual characteristics that explain interindividual variations in glucose disposal in response to a 6-month weight loss program in obese postmenopausal women. The cohort was divided into tertiles based on changes in glucose disposal after weight loss. Only women in the upper tertile (positive responders: Δ glucose disposal ≥ 0.92 mg/kg/min; n = 19) and lower tertile (negative responders: Δ glucose disposal ≤ -0.23 mg/kg/min; n = 19) were considered for analyses. Outcome measures included body weight, lean body mass (LBM), LBM index (= LBM / height [m]), fat mass (FM), FM index (= FM / height [m]), visceral fat, subcutaneous abdominal fat, high-sensitivity C-reactive protein (hsCRP) levels, interleukin-6, lipid profile, physical activity levels, fasting blood glucose and insulin levels, glucose disposal by hyperinsulinemic-euglycemic clamp technique, and resting blood pressure. At baseline, positive responders had higher triglycerides and hsCRP levels and lower glucose disposal (0.01 < P < 0.05) than negative responders. Except for visceral fat, the entire cohort showed significant decreases in all measures of body composition (P < 0.005) after weight loss, with greater decreases in body weight, body mass index, and FM index in positive responders (P < 0.005). Finally, data revealed that only positive responders showed decreases in LBM, LBM index, and hsCRP levels after weight loss (P between 0.01 and 0.001). An important interindividual variability in changes in glucose disposal after weight loss is observed. Interestingly, participants who display improvements in glucose disposal also show significant decreases in LBM, LBM index, and hsCRP after weight loss.

Lifestyle intervention involving calorie restriction with or without aerobic exercise training improves liver fat in adults with visceral adiposity.

Objective. To evaluate the effect of calorie restriction-induced weight loss with or without aerobic exercise on liver fat. Methods. Thirty-three adults with visceral adiposity were divided into calorie restriction (CR; n = 18) or CR and aerobic exercise (CR + Ex; n = 15) groups. Target energy intake was 25 kcal/kg of ideal body weight. The CR + Ex group had a targeted exercise time of 300 min/wk or more at lactate threshold intensity for 12 weeks. Results. Reductions in body weight (CR, −5.3 ± 0.8 kg; CR + Ex, −5.1 ± 0.7 kg), fat mass (CR, −4.9 ± 0.9 kg; CR + Ex, −4.4 ± 0.6 kg), and visceral fat (CR, −24 ± 5 cm2; CR + Ex, −37 ± 5 cm2) were not statistically different between groups. Liver fat decreased significantly in both groups, with no difference between groups. Change in maximal oxygen uptake was significantly greater in the CR + Ex group than in the CR group (CR, −0.7 ± 0.7 mL/kg/min; CR + Ex, 2.9 ± 1.0 mL/kg/min). Conclusion. Both CR and CR + Ex resulted in an improved reduction in liver fat; however, there was no additive effect of exercise training.

Weight Loss Improves the Adipogenic Capacity of Human Preadipocytes and Modulates Their Secretory Profile

Calorie restriction–induced weight loss is accompanied by profound changes in adipose tissue characteristics. To determine the effect of weight loss on differentiation of preadipocytes and secretory capacity of in vitro differentiated adipocytes, we established cultures of these cells from paired subcutaneous adipose tissue biopsies obtained before and at the end of weight-reducing dietary intervention (DI) in 23 obese women. Based on lipid accumulation and the expression of differentiation markers, in vitro adipogenesis increased after weight loss and it was accompanied by enhanced expression of genes involved in de novo lipogenesis. This effect of weight loss was not driven by changes of peroxisome proliferator–activated receptor γ sensitivity to rosiglitazone. Weight loss also enhanced the expression of adiponectin and leptin while reducing that of monocyte chemoattractant protein 1 and interleukin-8 by cultured adipocytes. Thus, the weight-reducing (DI) increased adipogenic capacity of preadipocytes and shifted their secretion toward lower inflammatory profile. Reprogramming of preadipocytes could represent an adaptation to weight loss leading to partial restoration of preobese adipose tissue traits and thus contribute to the improvement of metabolic status. However, enhanced adipogenesis could also contribute to the unwanted weight regain after initial weight loss.

Changes in Glucose Disposal After a Caloric Restriction-Induced Weight Loss Program in Obese Postmenopausal Women: Characteristics of Positive and Negative Responders

Changes in Glucose Disposal After a Caloric Restriction-Induced Weight Loss Program in Obese Postmenopausal Women: Characteristics of Positive and Negative Responders

Whey protein and essential amino acids promote the reduction of adipose tissue and increased muscle protein synthesis during caloric restriction-induced weight loss in elderly, obese individuals.

BackgroundExcess adipose tissue and sarcopenia presents a multifaceted clinical challenge that promotes morbidity and mortality in the obese, elderly population. Unfortunately, the mortality risks of muscle loss may outweigh the potential benefits of weight loss in the elderly. We have previously demonstrated the effectiveness of whey protein and essential amino acids towards the preservation of lean tissue, even under the conditions of strict bedrest in the elderly.MethodsIn the context of caloric restriction-based weight loss, we hypothesized that a similar formulation given as a meal replacement (EAAMR) would foster the retention of lean tissue through an increase in the skeletal muscle fractional synthesis rate (FSR). We also proposed that EAAMR would promote the preferential loss of adipose tissue through the increased energy cost of skeletal muscle FSR. We recruited and randomized 12 elderly individuals to an 8 week, caloric restriction diet utilizing equivalent caloric meal replacements (800 kcal/day): 1) EAAMR or a 2) competitive meal replacement (CMR) in conjunction with 400 kcal of solid food that totaled 1200 kcal/day designed to induce 7% weight loss. Combined with weekly measurements of total body weight and body composition, we also measured the acute change in the skeletal muscle FSR to EAAMR and CMR.ResultsBy design, both groups lost ~7% of total body weight. While EAAMR did not promote a significant preservation of lean tissue, the reduction in adipose tissue was greater in EAAMR compared to CMR. Interestingly, these results corresponded to an increase in the acute skeletal muscle protein FSR.ConclusionThe provision of EAAMR during caloric restriction-induced weight loss promotes the preferential reduction of adipose tissue and the modest loss of lean tissue in the elderly population.

Modulation of taste responsiveness and food preference by obesity and weight loss

Palatable foods lead to overeating, and it is almost a forgone conclusion that it is also an important contributor to the current obesity epidemic – there is even talk about food addiction. However, the cause–effect relationship between taste and obesity is far from clear. As discussed here, there is substantial evidence for altered taste sensitivity, taste-guided liking and wanting, and neural reward processing in the obese, but it is not clear whether such traits cause obesity or whether obesity secondarily alters these functions. Studies with calorie restriction-induced weight loss and bariatric surgery in humans and animal models suggest that at least some of the obesity-induced alterations are reversible and consequently represent secondary effects of the obese state. Thus, both genetic and non-genetic predisposition and acquired alterations in taste and reward functions appear to work in concert to aggravate palatability-induced hyperphagia. In addition, palatability is typically associated with high energy content, further challenging energy balance regulation. The mechanisms responsible for these alterations induced by the obese state, weight loss, and bariatric surgery, remain largely unexplored. Better understanding would be helpful in designing strategies to promote healthier eating and prevention of obesity and the accompanying chronic disease risks.