Caloric Restriction Research Articles

Time-Restricted Eating Versus Daily Calorie Restriction: Effect on Sleep in Adults with Obesity over 12 Months.

Objective: The aim of this secondary analysis was to compare the effects of time-restricted eating (TRE) versus daily calorie restriction (CR) on sleep quality, duration, insomnia severity, and risk of obstructive sleep apnea in adults with obesity over one year. Methods: A total of 90 participants were randomized to one of three groups for 12 months: 8 h TRE (eating only between 12 p.m. and 8 p.m.); CR (25% daily calorie restriction) or a no-intervention control group. Results: By the end of the study, weight loss was 4.61 kg (95% CI; 7.37 to 1.85 kg; p ≤ 0.01) for the TRE group and 5.42 kg (CI; 9.13 to 1.71 kg; p ≤ 0.01) for the CR group, with no statistically significant difference between TRE and CR (0.81 kg [CI; 3.07 to 4.69]; p = 0.68]). Self-reported sleep quality, sleep duration, insomnia severity, and risk of obstructive sleep apnea did not change in the TRE or CR groups versus controls by month 12. Conclusions: These findings suggest that the weight loss produced by TRE and CR does not have any impact on various sleep parameters in adults with obesity over one year.

Oral Administration of a Novel, Synthetic Ketogenic Compound Elevates Blood β-Hydroxybutyrate Levels in Mice in Both Fasted and Fed Conditions.

Elevating ketone levels with therapeutic nutritional ketosis can help to metabolically manage disease processes associated with epilepsy, diabetes, obesity, cancer, and neurodegenerative disease. Nutritional ketosis can be achieved with various dieting strategies such as the classical ketogenic diet, the modified Atkins diet, caloric restriction, periodic fasting, or the consumption of exogenous ketogenic supplements such as medium-chain triglycerides (MCTs). However, these various strategies can be unpleasant and difficult to follow, so that achieving and sustaining nutritional ketosis can be a major challenge. Thus, investigators continue to explore the science and applications of exogenous ketone supplementation as a means to further augment the therapeutic efficacy of this metabolic therapy. Here, we describe a structurally new synthetic triglyceride, glycerol tri-acetoacetate (Gly-3AcAc), that we prepared from glycerol and an acetoacetate precursor that produces hyperketonemia in the therapeutic range (2-3 mM) when administered to mice under both fasting and non-fasting conditions. Animal studies were undertaken to evaluate the potential effects of eliciting a ketogenic response systemically. Acute effects (24 h or less) were determined in male VM/Dk mice in both fasted and unfasted dietary states. Concentration levels of β-hydroxybutyrate in blood were elevated (βHB; 2-3 mM) under both conditions. Levels of glucose were reduced only in the fasted state. No detrimental side effects were observed. Pending further study, this novel compound could potentially add to the repertoire of methods for inducing therapeutic nutritional ketosis.

Is Fasting Superior to Continuous Caloric Restriction for Weight Loss and Metabolic Outcomes in Obese Adults? A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

fasting-based strategies (FBS) and continuous caloric restriction (CCR) are popular methods for weight loss and improving metabolic health. FBS alternates between eating and fasting periods, while CCR reduces daily calorie intake consistently. Both aim to create a calorie deficit, but it is still uncertain as to which is more effective for short- and long-term weight and metabolic outcomes. this systematic review and meta-analysis aimed to compare the effectiveness of FBS and CCR on these parameters in obese adults. after screening 342 articles, 10 randomized controlled trials (RCTs) with 623 participants were included. both interventions led to weight loss, with a reduction of 5.5 to 6.5 kg observed at the six-month mark. However, the results showed that FBS led to slightly greater short-term reductions in body weight (-0.94 kg, p = 0.004) and fat mass (-1.08 kg, p = 0.0001) compared to CCR, although these differences are not clinically significant. Both interventions had similar effects on lean mass, waist and hip circumference, blood pressure, lipid profiles, and glucose metabolism. However, FBS improved insulin sensitivity, with significant reductions in fasting insulin (-7.46 pmol/L, p = 0.02) and HOMA-IR (-0.14, p = 0.02). despite these short-term benefits, FBS did not show superior long-term outcomes compared to CCR. Both strategies are effective for weight management, but more research is needed to explore the long-term clinical relevance of FBS in obese populations.

Sustained caloric restriction potentiates insulin action by activating prostacyclin synthase.

Caloric restriction (CR) is known to enhance insulin sensitivity and reduce the risk of metabolic disorders; however, its molecular mechanisms are not fully understood. This study aims to elucidate specific proteins and pathways responsible for these benefits. We examined adipose tissue from participants in the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy Phase 2 (CALERIE 2) study, comparing proteomic profiles from individuals after 12 and 24 months of CR with baseline and an ad libitum group. Biochemical and cell-specific physiological approaches complemented these analyses. Our data revealed that CR upregulates prostacyclin synthase (PTGIS) in adipose tissue, an enzyme crucial for producing prostacyclin (PGI2). PGI2 improves the ability of insulin to stimulate the tether-containing UBX domain for GLUT4 (TUG) cleavage pathway, which is essential for glucose uptake regulation. Additionally, iloprost, a PGI2 analog, was shown to increase insulin receptor density on cell membranes, increasing glucose uptake in human adipocytes. CR also reduces carbonylation of GLUT4, a modification that is detrimental to GLUT4 function. CR enhances insulin sensitivity by promoting PTGIS expression and stimulating the TUG cleavage pathway, leading to increased GLUT4 translocation to the cell surface and decreased GLUT4 carbonylation. These findings shed light on the complex molecular mechanisms through which CR favorably impacts insulin sensitivity and metabolic health.

Maternal Malnutrition in Mice Impairs Nephrogenesis by Disrupting DNA Methylation of Regulatory Regions.

Maternal caloric restriction during pregnancy significantly impacts kidney development, influencing susceptibility to chronic kidney disease in adulthood. This study explores DNA methylation changes in nephron progenitor cells resulting from caloric restriction and their implications for kidney health. Global DNA hypomethylation is observed in nephron progenitors from caloric-restricted embryos, with specific genomic regions displaying distinct methylation patterns, including hypomethylation and hypermethylation. Differentially methylated regions exhibit enhanced chromatin accessibility, indicating biological relevance. Hypomethylated regions are enriched for genes associated with developmental processes, reflecting changes in gene expression and highlighting their functional relevance in kidney development. The study also reveals that supplementing methionine, an essential amino acid, restores disrupted DNA methylation patterns, particularly in enhancer regions, emphasizing methionine's critical role in regulating nephron progenitor cell epigenetics and ensuring proper kidney development. The intricate relationship between maternal nutrition, dynamic DNA methylation, and kidney development is highlighted, emphasizing the enduring impact of early-life nutritional challenges on kidney function. This research elucidates epigenetic mechanisms as mediators for the lasting effects of maternal caloric restriction on kidney health. The study contributes valuable insights into the origins of chronic kidney diseases during early developmental stages, offering potential interventions to mitigate adverse outcomes.

Interaction of Cooking-Generated Aerosols on the Human Nervous System and the Impact of Caloric Restriction Post-Exposure

Background: The inhalation of cooking-generated aerosols could lead to translocation to the brain and impact its function; therefore, the effects of cooking-generated aerosols on healthy adults were investigated using an electroencephalograph (EEG) during the 2 h period post-exposure. Methods: To explore any changes from the impact of exposure to cooking-generated aerosols on the human brain due to the absence of food intake during exposure, we divided the study participants into three groups: (A) no food intake for 2 h (2 h-zero calorie intake), (B) non-zero calorie intake, and (C) control group (simulated cooking). Results: The ultrafine particle concentrations increased from 9.0 × 103 particles/cm3 at the background level to approximately 8.74 × 104 particles/cm3 during cooking. EEGs were recorded before cooking (step 1), 60 min after cooking (step 2), 90 min after cooking (step 3), and 120 min after cooking (step 4). Comparing the non-zero calorie group with the control group, it was concluded that exposure to cooking-generated aerosols resulted in a 12.82% increase in the alpha band two hours post-exposure, compared to pre-exposure. The results revealed that zero calorie intake after exposure mitigated the impacts of cooking-generated aerosols for the alpha, beta3, theta, and delta bands, while it exacerbated effects on the whole brain for the beta1 and beta2 bands. Conclusions: While these are short-term studies, long-term exposure to cooking-generated ultrafine particles can be established through successive short-term exposures. These results underscore the need for further research into the health impacts of cooking-generated aerosols and the importance of implementing strategies to mitigate exposure.

Glucose metabolism in the perfused liver did not improve with resistance training in male Swiss mice under caloric restriction

Context: Energy homeostasis is a primary factor for the survival of mammals. Many tissues and organs, among which is the liver, keep this homeostasis in varied circumstances, including caloric restriction (CR) and physical activity. Objective: This study investigated glucose metabolism using the following groups of eight-week-old male Swiss mice: CS, sedentary and fed freely; RS, sedentary and RT, trained, both under 30% CR (n = 20–23 per group). Results: Organs and fat depots of groups RS and RT were similar to CS, although body weight was lower. CR did not impair training performance nor affected systemic or hepatic glucose metabolism. Training combined with CR (group RT) improved in vivo glucose tolerance and did not affect liver gluconeogenesis. Conclusions: The mice tolerated the prolonged moderate CR without impairment of their well-being, glucose homeostasis, and resistance training performance. But the higher liver gluconeogenic efficiency previously demonstrated using this training protocol in mice was not evidenced under CR.

Obesity Control and Supplementary Nutraceuticals as Cofactors of Brain Plasticity in Multiple Sclerosis Populations.

Multiple sclerosis (MS) is an immune-mediated disease characterized by inflammation, demyelination, and neurodegeneration within the central nervous system. Brain plasticity, the brain's ability to adapt its structure and function, plays a crucial role in mitigating MS's impact. This paper explores the potential benefits of lifestyle changes and nutraceuticals on brain plasticity in the MS population. Lifestyle modifications, including physical activity and dietary adjustments, can enhance brain plasticity by upregulating neurotrophic factors, promoting synaptogenesis, and reducing oxidative stress. Nutraceuticals, such as vitamin D, omega-3 fatty acids, and antioxidants like alpha lipoic acid, have shown promise in supporting brain health through anti-inflammatory and neuroprotective mechanisms. Regular physical activity has been linked to increased levels of brain-derived neurotrophic factor and improved cognitive function. Dietary interventions, including caloric restriction and the intake of polyphenols, can also positively influence brain plasticity. Integrating these lifestyle changes and nutraceuticals into the management of MS can provide a complementary approach to traditional therapies, potentially improving neurological outcomes and enhancing the quality of life for the MS population.

Dietary restriction impacts health and lifespan of genetically diverse mice.

Caloric restriction extends healthy lifespan in multiple species1. Intermittent fasting, an alternative form of dietary restriction, is potentially more sustainable in humans, but its effectiveness remains largely unexplored2-8. Identifying the most efficacious forms of dietary restriction is key for developing interventions to improve human health and longevity9. Here we performed an extensive assessment of graded levels of caloric restriction (20% and 40%) and intermittent fasting (1 and 2 days fasting per week) on the health and survival of 960 genetically diverse female mice. We show that caloric restriction and intermittent fasting both resulted in lifespan extension in proportion to the degree of restriction. Lifespan was heritable and genetics had a larger influence on lifespan than dietary restriction. The strongest trait associations with lifespan included retention of body weight through periods of handling-an indicator of stress resilience, high lymphocyte proportion, low red blood cell distribution width and high adiposity in late life. Health effects differed between interventions and exhibited inconsistent relationships with lifespan extension. 40% caloric restriction had the strongest lifespan extension effect but led to a loss of lean mass and changes in the immune repertoire that could confer susceptibility to infections. Intermittent fasting did not extend the lifespan of mice with high pre-intervention body weight, and two-day intermittent fasting was associated with disruption of erythroid cell populations. Metabolic responses to dietary restriction, including reduced adiposity and lower fasting glucose, were not associated with increased lifespan, suggesting that dietary restriction does more than just counteract the negative effects of obesity. Our findings indicate that improving health and extending lifespan are not synonymous and raise questions about which end points are the most relevant for evaluating aging interventions in preclinical models and clinical trials.

Molecular characterization and expression pattern analysis of Sirtuin family genes in the eastern honeybee, Apis cerana

Sirtuin proteins are a family of evolutionarily conserved NAD+-dependent deacetylase enzymes which play crucial roles in regulating insect metabolism, maintaining genome stability, and lifespan. However, there is no report on the genome-wide analysis of the Sirtuin gene family in the eastern honeybee, Apis cerana. Here, 6 Sirtuin genes (AcSirt1, AcSirt2, AcSirt4 ~ AcSirt7) were obtained in the A. cerana genome, which were located on 6 different chromosomes and were all single-copy genes. Gene structure analysis revealed that these 6 genes were all multi-exon genes. The Sirtuin family genes contained 9 conserved motifs and 5 conserved domains, which exhibited typical Sirtuin protein structural characteristics. The phylogenetic analysis of the Sirtuin family genes indicates that A. cerana lacked the Sirt3 gene, and the 6 Sirtuin encoding genes could be clustered into 5 groups and 6 branches, showing high homology with the Apis mellifera and the Apis dorsata. The results of the tissue and period expression profiles by qRT-PCR indicated that the 6 Sirtuin family genes showed transcriptional activity in different tissues of worker bees, and the gene expression level reached the peak in the 4-day-old larvae and pupa stages. It was speculated that Sirtuin genes expression level was affected by fasting behavior, caloric restriction and organ differentiation during different developmental stages of A. cerana. Meanwhile, the differential expression patterns of Sirtuin genes in various tissues further demonstrated the diversity and complexity of their functions, providing a basis for target selection in future studies on the functionality of Sirtuin genes.

A whole food, plant-based diet reduces amino acid levels in patients with metastatic breast cancer.

Amino acids are critical to tumor survival. Tumors can acquire amino acids from the surrounding microenvironment, including the serum. Limiting dietary amino acids is suggested to influence their serum levels. Further, a plant-based diet is reported to contain fewer amino acids than an animal-based diet. Here, we investigated the impact of a whole food, plant-based diet on lowering the serum levels of amino acids in patients with cancer. Patients with metastatic breast cancer (n=18) were enrolled in clinical trial NCT03045289 . An ad libitum whole food, plant-based diet was implemented for 8 weeks without calorie or portion restriction. We found that a whole food, plant-based diet resulted in a lower intake of calories, fat, and amino acids and higher levels of fiber. Additionally, body weight, serum insulin, and IGF-1 were reduced in participants. The diet contained lower levels of essential and non-essential amino acids. Importantly, the lowered dietary intake of amino acids translated to reduced serum levels of amino acids in participants (5/9 essential amino acids; 4/11 non-essential amino acids). These findings provide a tractable approach to limiting amino acid levels in cancer patients. This data lays a foundation for studying the relationship between amino acids in patients and tumor progression. Further, a whole-food, plant-based diet has the potential to synergize with cancer therapies that exploit metabolic vulnerabilities.

Resting Energy Expenditure in Patients with Extreme Obesity: Comparison of the Harris-Benedict Equation with Indirect Calorimetry.

Background: The main objective of the work was the analysis and description of data on body composition and resting energy expenditure (REE) values of selected groups of patients with obesity whose REE measurement results using indirect calorimetry reached a level below 95% of the predicted REE calculated using the Harris-Benedict (H-B) equation. The sub-goals were to describe the dependence of body composition on the size of the REE and to find out if the deviations between the number of the total measured REE and the REE calculated using H-B in the adapted group (patients with altered REE values, lower than expected caused by long caloric restriction) are significant. Methods: For the research, 71 (39 women and 32 men) patients treated in obesitology were selected. Patients underwent the measurement of resting metabolism using indirect calorimetry (IC) and body composition measurement on the bioimpedance device and, at the same time, the value of resting metabolism was calculated for everyone using the H-B equation. The whole group was divided into five groups according to the deviation of the measurement using IC and the calculation of the H-B equation. Results: In the total set of examined individuals, there were 32.4% with a reduced REE value compared to the REE calculation according to the H-B equation, which corresponds to 23 individuals. In the adapted group, the average measured REE was 2242 ± 616 kcal compared to the H-B calculation of 2638 ± 713 kcal. Statistically, these results were not significant, but a high case-to-case variation was found. The highest deviation from the H-B predictive calculation was -42% and +43% in the whole research group. The amount of muscle tissue in the adapted group averaged 44.3 ± 11.9 kg and the amount of fat-free mass (FFM) 77.9 ± 20.1 kg. When statistically testing the dependence of REE on FFM and muscle tissue in the adapted group, a strong correlation was found. Conclusions: The H-B equation alone is not suitable for setting a suitable diet therapy for an individual with obesity. In order to select and characterize a group of adapted individuals, it will be necessary to use other methods or a larger research sample, and preferably examine and divide patients with specific comorbidities or include their health status.

7943 In Obese C57Bl6 Male Mice, Weight Loss due to Caloric Restriction Reduced Bone Morphology but Improved Components of Systemic Metabolism

Abstract Disclosure: C. Chlebek: None. C. McAndrews: None. S.N. Costa: None. C.J. Rosen: None. Obesity and calorie restriction individually alter systemic cellular metabolism and affect musculoskeletal tissue health. Obesity reduces trabecular and cortical bone quality. Clinically, obese patients are advised to lose weight, despite the negative effects of calorie restriction on bone in nonobese preclinical models. Little is known about bone quality following weight loss in obese preclinical models. We hypothesized that in obese models, caloric restriction would further worsen bone quality. To induce obesity, male C57Bl6 mice (8 weeks old) received 60% high fat diet for 12 weeks (high fat feeding phase). Following obesity induction, the HFD-CR group was acclimated to control low fat diet for 2 wks and then underwent 30% caloric restriction for 8 wks (caloric restriction feeding phase). The HFD group received 60% kcal high fat diet from ages 8 to 30 wks. LFD mice received control low fat 10% kcal diet for the study duration. Mice were euthanized at 30 wks of age. Body weight, body composition, and bone mineral density were recorded at baseline and at the end of each diet. Glucose and insulin tolerance were recorded at the end of the high fat and caloric restriction feeding phases. At euthanasia, cortical and trabecular bone morphology (µCT) were assessed.Adverse metabolic parameters worsened with high fat feeding but improved by caloric restriction. Compared to LFD animals, HFD and HFD-CR mice gained body weight, fat mass, and lean mass during the high fat feeding phase. After the caloric restriction feeding phase, body weight, fat mass, and lean mass were reduced in HFD-CR compared to both HFD and LFD controls (p < 0.0001). After 12 weeks of high fat feeding, glucose and insulin tolerance were reduced in HFD and HFD-CR mice compared to LFD (p < 0.0001). Caloric restriction improved both glucose and insulin tolerance in HFD-CR mice compared to both HFD and LFD animals (p < 0.0001). Caloric restriction improved areal bone mineral density, but at euthanasia, HFD-CR mice had worse bone morphology compared to LFD or HFD animals. Although areal bone mineral density (aBMD) was reduced by the high fat feeding phase, HFD-CR and LFD aBMD was not different at the end of the study (p < 0.0001). At euthanasia, HFD-CR mice had reduced cortical area and cortical thickness (p < 0.05). Marrow area and moment of inertia were not different between diets. Compared to LFD, both HFD and HFD-CR mice had reduced tibial bone volume fraction (p < 0.05). HFD-CR animals had smaller trabecular thickness (p < 0.05) and greater trabecular number (p < 0.01) compared to HFD mice. Despite improvements in components of systemic metabolism, caloric restriction in obese preclinical models reduced bone morphology in both trabecular and cortical compartments. This work will improve our understanding of the musculoskeletal system following caloric restriction in obese models and will aid in nutritional counseling for obese patients. Presentation: 6/1/2024

Effects of Human Milk Oligosaccharide 2′-Fucosyllactose Ingestion on Weight Loss and Markers of Health

Background: 2′-Fucosyllactose (2′-FL) is an oligosaccharide contained in human milk and possesses prebiotic and anti-inflammatory effects, which may alleviate skeletal muscle atrophy under caloric restriction. This study evaluated the impacts of 12 weeks of 2′-FL supplementation in conjunction with exercise (10,000 steps/day, 5 days/week) and energy-reduced (−300 kcals/day) dietary interventions on changes in body composition and health-related biomarkers. Methods: A total of 41 overweight and sedentary female and male participants (38.0 ± 13 years, 90.1 ± 15 kg, 31.6 ± 6.6 kg/m2, 36.9 ± 7% fat) took part in a randomized, double-blind, and placebo-controlled study. The participants underwent baseline assessments and were then assigned to ingest 3 g/day of a placebo (PLA) or Momstamin 2′-F while initiating the exercise and weight-loss program. Follow-up tests were performed after 6 and 12 weeks. Data were analyzed using general linear model statistics with repeated measures and mean changes from baseline values with 95% confidence intervals (CIs). Results: No group × time × sex interaction effects were observed, so group × time effects are reported. Participants in both groups saw comparable reductions in weight. However, those with 2′-FL demonstrated a significantly greater reduction in the percentage of body fat and less loss of the fat-free mass. Additionally, there was evidence that 2′-FL supplementation promoted more favorable changes in resting fat oxidation, peak aerobic capacity, IL-4, and platelet aggregation, with some minimal effects on the fermentation of short-chain fatty acids and monosaccharides in fecal samples. Moreover, participants’ perceptions regarding some aspects of the functional capacity and ratings of the quality of life were improved, and the supplementation protocol was well tolerated, although a small, but significant, decrease in BMC was observed. Conclusions: The results support contentions that dietary supplementation of 2′-FL (3 g/d) can promote fat loss and improve exercise- and diet-related markers of health and fitness in overweight sedentary individuals initiating an exercise and weight-loss program. Further research is needed to explore the potential health benefits of 2′-FL supplementation in both healthy and elderly individuals (Registered clinical trial #NCT06547801).

From starvation to time-restricted eating: a review of fasting physiology.

We have long known that subjects with obesity who fast for several weeks survive. Calculations that assume the brain can only use glucose indicated that all carbohydrate and protein sources would be consumed by the brain within several weeks yet subjects with obesity who fasted for several weeks survived. This anomaly led to the determination of the metabolic role of ketone bodies. Subsequent studies transformed our understanding of ketone bodies and illustrated the value of challenging the norm and adapting theory to evidence. Although prolonged fasting is no longer a treatment for obesity, the early studies of starvation provided valuable insights about macronutrient metabolism and ketone body adaptations that fasting elicits. Intermittent fasting and its variants such as time-restricted eating are fasting models that are far less regimented than starvation and severe calorie restriction; yet they produce metabolic benefits. The mechanisms that produce the metabolic changes that intermittent fasting elicits are relatively unknown. In this article, we review the physiology of starvation, starvation adaptation diets, diet-induced ketosis, and intermittent fasting. Understanding the premise and physiology that these regimens induce is necessary to draw parallels and provoke thoughts on the mechanisms underlying the metabolic benefits of intermittent fasting and its variants.

Insulin resistance reduction, intermittent fasting, and human growth hormone: secondary analysis of a randomized trial

Intense intermittent fasting regimens safely reduce weight to a similar extent as caloric restriction. A previous trial reported low-frequency 26-week intermittent fasting reduced homeostatic model assessment of insulin resistance (HOMA-IR) without significant weight loss. During fasting, human growth hormone (HGH) increases substantially, but whether basal HGH modifies the effect of fasting on outcomes of repeated fasting is unknown. In a post hoc analysis of a randomized controlled trial (registration: clinicaltrials.gov, NCT02770313, May 12, 2016), subjects (N = 68) were adults ages 21–70 years with modest cholesterol elevation, ≥1 metabolic syndrome component, available HGH measurements, no chronic disease, and no statin or anti-diabetes medication. Randomization was 1:1 to intermittent fasting (24-hour, water-only, twice-per-week for 4 weeks, then once-per-week for 22 weeks) or 26-week ad libitum control. General linear modeling evaluated the interaction of trial arm with baseline HGH for HOMA-IR changes. Subjects with lower baseline HGH had 26-week HOMA-IR changes (p = 0.003) of −1.04 ± 0.99 for fasting versus 0.60 ± 1.04 for controls. Subjects with higher baseline HGH had HOMA-IR changes (p = 0.26) of −0.69 ± 0.75 (fasting) and −0.42 ± 0.92 (controls). The interaction of fasting with lower baseline HGH was significant (p-interaction=0.004). Results were similar for insulin and glucose. Weight loss at 26 weeks was not significantly different between fasting and controls (−1.74 ± 4.81 kg vs. 0.21 ± 3.50 kg, p = 0.08) and was not correlated with changes in HOMA-IR, insulin, glucose, and HGH. In conclusion, lower baseline HGH modified the effect of low-frequency water-only 24-hour fasting in profoundly reducing HOMA-IR over 26 weeks compared both to controls and to fasting subjects with higher baseline HGH.

Randomized study of the effects of empagliflozin and topiramate dual therapy on anthropometric and metabolic indices in non-diabetic individuals with overweight/obesity on a calorie-restricted diet

ObjectivesThe objective of this study was to evaluate the effectiveness of the combined use of empagliflozin (EMPA) and topiramate (TPM) versus a placebo in overweight/obese individuals without diabetes on a calorie-restricted diet.MethodsIn this study, 44 non-diabetic and overweight/obese subjects who were on a calorie restricted diet were randomly assigned into 2 groups: (1) Participants received a 10 mg EMPA tablet daily plus TPM tablet (at the 1st week 25 mg once a day and from the second week 25 mg twice a day); (2) Participants received an empagliflozin placebo (daily) plus a topiramate placebo (as mentioned for topiramate tablet in group 1), for 12 weeks. At baseline and weeks 4, 8, 12, weight, height, body mass index (BMI), waist circumference (WC), and body composition were evaluated. Before and after the intervention, blood pressure, C reactive protein, and glucose and lipid profile parameters were measured.ResultsThe EMPA/TPM group, compared to placebo, had a greater percent change of weight at week 12 (− 8.92 ± 1.80 vs. − 4.93 ± 1.17). The intervention group had a greater percent change of fat mass and fat percent at week 12 (P < 0.05). However, there was no difference in the percent of change in fat-free percent between the two groups at week 12 (P = 0.577). Within-group analysis found a significant reduction in SBP, DBP, FBS, insulin, HOMA-IR, TC, LDL, HDL, TG, and CRP in both groups (P < 0.05). At week 12, no statistically significant difference was observed between the two groups in any of mentioned variables (P > 0.05).ConclusionIn non-diabetic overweight/obese individuals, the combination of EMPA/TPM and calorie restriction led to a notable decrease in body weight and was generally well-tolerated. Further research is required to evaluate the potential advantages of utilizing this combination for sustained weight management in the long run.Level I Randomized clinical trial.

Revealing motor insensitivity to food in Anorexia Nervosa as a potential mechanism contributing to calorie restriction: A mobile Approach Avoidance Task study

A change in implicit behavioural tendencies toward foods may contribute to the maintenance of calorie restriction in Anorexia Nervosa (AN). To test this hypothesis, we assessed approach-avoidance tendencies toward different categories of stimuli using a novel mobile version of the approach-avoidance task (AAT). The sample included 66 patients with restrictive AN and 84 healthy controls, all females. All participants performed the AAT in which they were required to approach or avoid stimuli (high-calorie foods, low-calorie foods, and neutral objects) by respectively pulling their phone towards themselves of pushing it away. Both the response time and the force of each movement were collected by means of the smartphone's accelerometer. The results revealed that patients with AN had a reduced tendency to approach food stimuli compared to healthy controls, who instead presented faster and stronger movements in approaching rather than avoiding foods as compared to neutral objects. This finding was particularly pronounced in patients with greater levels of malnutrition. No differences were instead observed comparing high-calorie and low-calorie foods. The observed reduction in the natural tendency to approach food stimuli is consistent with patients' eating behaviour and may contribute to the maintenance of calorie restriction, thus representing a possible target for novel therapeutic approaches.

Effects of caloric restriction with different doses of exercise on fat loss in people living with type 2 diabetes: A secondary analysis of the DOSE-EX randomized clinical trial

BackgroundFat loss mainly conveys the benefits of caloric restriction for people living with type 2 diabetes. The literature is equivocal regarding whether exercise facilitates fat loss during caloric restriction. This analysis aimed to assess the dose–response effects of exercise in combination with a caloric restriction on fat mass (FM) and FM percentage (FM%) in persons with diagnosed type 2 diabetes. MethodsIn this secondary analysis of a 4-armed randomized trial, 82 persons living with type 2 diabetes were randomly allocated to the control group (CON) (n = 21), diet control (DCON) (25% caloric restriction; n = 20), diet control and exercise 3 times per week (MED) (n = 20), or diet control and exercise 6 times per week (HED) (n = 21) for 16 weeks. The primary analysis was the change in FM% points. Secondary analyses included fat-free mass and visceral adipose tissue (VAT) volume (cm3). ResultsFM% decreased compared to CON by a mean difference of –3.5% (95% confidence interval (95%CI): –5.6% to –1.4%), –6.3% (95%CI: –8.4% to –4.1%), and –8.0% (95%CI: –10.2% to –5.8%) for DCON, MED, and HED, respectively. Compared to DCON, MED and HED decreased FM% by –2.8% (95%CI: –4.9% to –0.7%) and –4.5% (95%CI: –6.6% to –2.4%), respectively. The difference in FM% between HED and MED was –1.8% (95%CI: –3.9% to 0.4%). DCON and MED decreased fat-free mass compared to CON, whereas HED preserved fat-free mass (–0.2% (95%CI: –2.0% to 1.7%)). Compared to CON, VAT volume decreased by –666.0 cm3 (95%CI: –912.8 cm3 to –385.1 cm3), –1264.0 (95%CI: –1679.6 cm3 to –655.9 cm3), and –1786.4 cm3 (95%CI: –2264.6 cm3 to –1321.2 cm3) more for DCON, MED, and HED, respectively. HED decreased VAT volume more than DCON (–1120.4 cm3 (95%CI: –1746.6 cm3 to –639.4 cm3)) while the remaining comparisons did not reveal any differences. ConclusionAll interventions were superior in reducing FM% compared to standard care. Adding exercise to a caloric restriction was superior in reducing FM% compared to a caloric restriction alone.

Calorie restriction modulates mitochondrial dynamics and autophagy in leukocytes of patients with obesity

Although it is established that caloric restriction offers metabolic and clinical benefits, the molecular mechanisms underlying these effects remain unclear. Thus, this study aimed to investigate whether caloric restriction can modulate mitochondrial function and remodelling and stimulate autophagic flux in the PBMCs of patients with obesity. This was an interventional study of 38 obese subjects (BMI > 35 kg/m2) who underwent 6 months of dietary therapy, including a 6-week very-low-calorie diet (VLCD) followed by an 18-week low-calorie diet (LCD). We determined clinical variables, mitochondrial function parameters (by fluorescence imaging of mitochondrial ROS and membrane potential), and protein expression of markers of mitochondrial dynamics (MNF1, MFN2, OPA, DRP1 and FIS1) and autophagy (LC3, Beclin, BCL2 and NBR1) by western blot. Caloric restriction induced an improvement in metabolic outcomes that was accompanied by an increase in AMPK expression, a decrease of mitochondrial ROS and mitochondrial membrane potential, which was associated with increased markers of mitochondrial dynamics (MFN2, DRP1 and FIS1) and activation of autophagy as evidenced by augmented LC3 II/I, Beclin1 and NBR1, and a decrease in BCL2. These findings shed light on the specific molecular mechanisms by which caloric restriction facilitates metabolic improvements, highlighting the relevance of pathways involving energy homeostasis and cell recovery, including mitochondrial function and dynamics and autophagy.