Histological improvements following energy restriction and exercise: The role of insulin resistance in resolution of MASH.

BACKGROUND & AIMS: Metabolic dysfunction-associated steatohepatitis (MASH) is one of the most common liver diseases worldwide and is characterized by multi-tissue insulin resistance. The effects of a 10-month energy restriction and exercise intervention on liver histology, anthropometrics, plasma biochemistries, and insulin sensitivity were compared to standard of care (control) to understand mechanisms that support liver health improvements. METHODS: Following medical diagnosis of MASH, individuals were randomized to treatment (n = 16) or control (n = 8). Liver fat (magnetic resonance spectroscopy), 18-hour plasma biochemical measurements, and isotopically labeled hyperinsulinemic-euglycemic clamps were completed pre- and post-intervention. Body composition and cardiorespiratory fitness (VO2peak) were also measured mid-intervention. Those in the treatment group were counseled to reduce energy intake and completed supervised, high-intensity interval training (3x/week) for 10 months. Controls continued physician-directed care. RESULTS: Treatment induced significant (p <0.05) reductions in body weight, fat mass, and liver injury, while VO2peak (p <0.05) and non-esterified fatty acid suppression (p = 0.06) were improved. Both groups exhibited reductions in total energy intake, hemoglobin A1c, hepatic insulin resistance, and liver fat (p <0.05). Compared to control, treatment induced a two-fold increase in peripheral insulin sensitivity which was significantly related to higher VO2peak and resolution of liver disease. CONCLUSIONS: Exercise and energy restriction elicited significant and clinically meaningful treatment effects on liver health, potentially driven by a redistribution of excess nutrients to skeletal muscle, thereby reducing hepatic nutrient toxicity. Clinical guidelines should emphasize the addition of aerobic exercise in lifestyle treatments for the greatest histologic benefit in individuals with advanced MASH. IMPACT AND IMPLICATIONS: The mechanisms that underpin histologic improvement in individuals with metabolic dysfunction-associated steatohepatitis (MASH) are not well understood. This study evaluated the relationship between liver and metabolic health, testing how changes in one may affect the other. We investigated the effects of energy restriction and exercise on the association between multi-tissue insulin sensitivity and histologic improvements in participants with biopsy-proven MASH. For the first time, these results show that an improvement in peripheral (but not hepatic) insulin sensitivity and systemic markers of muscle function (i.e. cardiorespiratory fitness) were strongly related to resolution of liver disease. Extrahepatic disposal of substrates and improved fitness levels supported histologic improvement, confirming the addition of exercise as crucial to lifestyle interventions in MASH. CLINICAL TRIAL NUMBER: NCT03151798.

Intermittent energy restriction inhibits tumor growth and enhances paclitaxel response in a transgenic mouse model of endometrial cancer.

OBJECTIVE: Overweight/obesity is the strongest risk factor for endometrial cancer (EC), and weight management can reduce that risk and improve survival. We aimed to establish the differential benefits of intermittent energy restriction (IER) and low-fat diet (LFD), alone and in combination with paclitaxel, to reverse the procancer effects of high-fat diet (HFD)-induced obesity in a mouse model of EC. METHODS: Lkb1fl/flp53fl/fl mice were fed HFD or LFD to generate obese and lean phenotypes, respectively. Obese mice were maintained on a HFD or switched to a LFD (HFD-LFD) or IER (HFD-IER). Ten weeks after induction of endometrial cancer, mice in each group received paclitaxel or placebo for 4 weeks. Body and tumor weights; tumoral transcriptomic, metabolomic and oxylipin profiles; and serum metabolic hormones and chemocytokines were assessed. RESULTS: HFD-IER and HFD-LFD, relative to HFD, reduced body weight; reversed obesity-induced alterations in serum insulin, leptin and inflammatory factors; and decreased tumor incidence and mass, often to levels emulating those associated with continuous LFD. Concurrent paclitaxel, versus placebo, enhanced tumor suppression in each group, with greatest benefit in HFD-IER. The diets produced distinct tumoral gene expression and metabolic profiles, with HFD-IER associated with a more favorable (antitumor) metabolic and inflammatory environment. CONCLUSION: In Lkb1fl/flp53fl/fl mice, IER is generally more effective than LFD in promoting weight loss, inhibiting obesity-related endometrial tumor growth (particularly in combination with paclitaxel), and reversing detrimental obesity-related metabolic effects. These findings lay the foundation for further investigations of IER as an EC prevention and treatment strategies in overweight/obesity women.

A very-low-calorie ketogenic diet normalises obesity-related enhanced levels of erythropoietin compared with a low-calorie diet or bariatric surgery.

PURPOSE: Nutritional ketosis synergistically with body-weight loss induced by a very-low-calorie ketogenic diet (VLCKD) has proven to be effective in improving obesity-related pathophysiology. Recently, growing attention has been focused on the relation between erythropoietin (EPO) and obesity. Thus, this study aims to investigate whether nutritional ketosis and weight loss induced by a VLCKD modify the circulating levels of EPO in patients with obesity in comparison with the effect of low-calorie diet (LCD) or bariatric surgery (BS). METHODS: EPO levels, iron status and body composition parameters were evaluated in 72 patients with overweight or obesity and 27 normal-weight subjects at baseline and after the three different weight-reduction therapies (VLCKD, LCD and BS) in 69 patients with excess body weight. ß-hydroxybutyrate levels were also measured in the VLCKD group. The follow-up was established at 2-3 months and 4-6 months. RESULTS: It was found that EPO levels were higher in morbid obesity and correlated with higher basal weight, fat mass (FM) and fat-free mass (FFM) in the overall sample. High baseline EPO levels were also correlated with higher impact on the course of weight loss and changes in FM and FFM induced by the three weight-loss interventions. Furthermore, the VLCKD induced a decrease in EPO levels coinciding with maximum ketosis, which was maintained over time, while statistically significant changes were not observed after LCD and BS. CONCLUSION: The obesity-related increased EPO levels are restored after VLCKD intervention at the time of maximum ketosis, suggesting a potential role of the nutritional ketosis induced by the VLCKD. Baseline EPO levels could be a biomarker of response to a weight-loss therapy.

Effects of energy-restricted diets with or without nuts on weight, body composition and glycaemic control in adults: a scoping review.

Energy-restricted (ER) diets promote weight loss and improve body composition and glycaemic control. Nut consumption also improves these parameters. However, less is known about the combined benefit of these two strategies. This scoping review implemented a systematic search of Medline, Embase and Scopus to identify randomised controlled trials evaluating the effect of ER diets with or without nuts on body mass, body composition and glycaemic control in adults. After reviewing titles and abstracts, twenty-nine full-text articles were screened, resulting in seven studies reported in eight papers that met the inclusion criteria. Energy restriction was achieved by prescribing a set energy target or reducing intake by 1000-4200 kJ from daily energy requirements. Interventions ranged from 4 to 52 weeks in duration and contained 42-84 g/d of almonds, peanuts, pistachios or walnuts. While all studies reported that energy restriction resulted in significant weight loss, the addition of nuts to ER diets demonstrated significantly greater weight loss in only approximately half of the included studies (4/7 studies). There was limited evidence to support additional benefits from nuts for body composition measures or glycaemic control. Although improvements in weight loss and glycaemia were not consistent when nuts were included in ER diets, no study revealed an adverse effect of nut consumption on health outcomes. Future studies could explore the effect of consuming different types and amounts of nuts, combined with various levels of energy restriction on weight, body composition and glycaemic control.

Energy availability modulates regional blood flow via estrogen-independent pathways in regularly menstruating young women.

PURPOSE: This study aimed to investigate the impact of short-term low energy availability (LEA) on vascular function in young, regularly menstruating women. METHODS: Participants were 19 women, aged 22.9 ± 4.2 years, with body mass index 18-30 kg·m2. They were divided into two groups and completed two conditions in a crossover design: a 3-day control condition (CON) with an energy availability of 45 kcals·kgFFM-1·day-1 and a 3-day LEA condition of 15 kcals·kgFFM-1 day-1. Assessments were conducted during the early follicular phase of the menstrual cycle. Outcome measures included forearm blood flow (FBF), heart rate, blood pressure, arterial stiffness, resting energy expenditure (REE), metabolic blood markers and body composition. RESULTS: Significant time-by-condition interactions were found for resting FBF (p = .004), REE (p = .042), triiodothyronine (p = .006), ß-hydroxybutyrate (p = .002) and body mass (p < .001). Resting FBF was 1.43 ± 1.01 and 1.31 ± 0.61 (arbitrary units) at pre and post, respectively, in LEA and 1.52 ± 0.7 and 1.76 ± 0.57 at pre and post in CON. The LEA condition led to a decrease in triiodothyronine (pre: 1.54 ± 0.28, post: 1.29 ± 0.27 ng ml-1), REE (pre: 1588 ± 165, post: 1487 ± 160 kcals day-1) and body mass (pre: 61.4 ± 7.5, post: 59.6 ± 7.3 kg). Changes in resting FBF were significantly correlated with changes in REE in the LEA condition (r = 0.53; p = 0.02). CONCLUSION: Short-term LEA modifies regional blood flow and this might contribute to the observed decreased in REE. Findings emphasize the need for careful management of energy availability in populations at risk of LEA.

Interindividual variability in energy intake and expenditure during a weight loss intervention.

INTRODUCTION: Behavioral compensations may occur as a response to a negative energy balance. The aim of this study was to explore the associations between changes in energy intake (EI) and changes in physical activity (PA, min/day; kcal/d) as a response to a weight loss (WL) intervention and to understand if interindividual differences occur in EI and energy expenditure (EE). METHODS: Eighty-one participants [mean (SD): age = 42.8 (9.4)y, BMI = 31.2 (4.4)kg/m2, 37% females] divided in intervention (IG, n = 43) and control group (CG, n = 38) were included. The IG underwent a moderate energy restriction (300-500 kcal/d). EI was measured through the intake-balance method. Non-exercise PA (NEPA) and exercise (through logbook) were assessed by accelerometery. The EE in NEPA (NEAT) and in exercise (EiEE) was calculated by applying the Freedson Combination'98 algorithm over the time spent in these activities. Pearson correlations were performed in IG to examine associations between EE components, EI and body composition. To understand if interindividual differences were observed, the SD of individual response (SDIR) and the smallest worthwhile change (SWC, SDbaselineCG×0.2) were calculated. RESULTS: Changes in EI [Δ EI, (kcal/d)] was negatively associated with Δ exercise (min/d:r = -0.413, p = 0.045; %:r = -0.846, p = 0.008) and with Δ EiEE (kcal/d:r = -0.488, p = 0.016; %:r = -0.859, p = 0.006). A negative correlation was found between Δ sedentary time and Δ NEPA (min/d:r = -0.622, p = 0.002; %:r = -0.487, p = 0.018). An interindividual variability was found for EI(SDIR = 151.6, SWC = 72.3) and EE (SDIR = 165, SWC = 134). CONCLUSIONS: Decreases in EI were not associated to compensatory responses such as decreases in PA and/or increases in sedentary time. Interindividual variability was found for EI and EE. Nevertheless, behavioral compensations and the interindividual variability should be considered when implementing WL interventions, to increase the likelihood of achieving sustainable results. (clinicaltrials.gov ID: NCT03031951).

Comparative efficacy of energy-restricted dietary interventions in overweight and obese populations: A systematic review and network meta-analysis.

This meta-analysis compared the effectiveness of different energy-restricted diets on body composition, glucose metabolism, and lipid metabolism in overweight and obese populations. Five databases were searched to identify relevant studies in English from inception until July 20, 2023, for randomized controlled trials of at least 2 weeks duration assessing the effects of continuous energy-restricted diets compared with any intermittent energy-restricted diet in obesity adults. The risk of bias was assessed using the Cochrane Risk of Bias Tool version 2.0, while the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) system was used to assess the certainty of the evidence. A non-informative prior distribution Bayesian network meta-analysis was conducted. Thirty-eight studies (3039 participants) assessing four energy-restricted diets were included. Three RCTs were at high risk of bias with a very low to moderate certainty of evidence. Combined with pairwise comparisons and surface under the cumulative ranking curve, alternate-day fasting may be the best energy restriction regimen with the potential to have the most beneficial effects on various aspects of the obesity population. More rigorously designed and long-term follow-up studies are warranted.

Low energy availability reduces myofibrillar and sarcoplasmic muscle protein synthesis in trained females.

Low energy availability (LEA) describes a state where the energy intake is insufficient to cover the energy costs of both exercise energy expenditure and basal physiological body functions. LEA has been associated with various physiological consequences, such as reproductive dysfunction. However, the effect of LEA on skeletal muscle protein synthesis in females performing exercise training is still poorly understood. We conducted a randomized controlled trial to investigate the impact of LEA on daily integrated myofibrillar and sarcoplasmic muscle protein synthesis in trained females. Thirty eumenorrheic females were matched based on training history and randomized to undergo 10 days of LEA (25 kcal · kg fat-free mass (FFM)-1  · day-1 ) or optimal energy availability (OEA, 50 kcal · kg FFM-1  · day-1 ). Before the intervention, both groups underwent a 5-day 'run-in' period with OEA. All foods were provided throughout the experimental period with a protein content of 2.2 g kg lean mass-1  · day-1 . A standardized, supervised combined resistance and cardiovascular exercise training programme was performed over the experimental period. Daily integrated muscle protein synthesis was measured by deuterium oxide (D2 O) consumption along with changes in body composition, resting metabolic rate, blood biomarkers and 24 h nitrogen balance. We found that LEA reduced daily integrated myofibrillar and sarcoplasmic muscle protein synthesis compared with OEA. Concomitant reductions were observed in lean mass, urinary nitrogen balance, free androgen index, thyroid hormone concentrations and resting metabolic rate following LEA. These results highlight that LEA may negatively affect skeletal muscle adaptations in females performing exercise training. KEY POINTS: Low energy availability (LEA) with potential health and performance impairments is widespread among female athletes. We investigated the impact of 10 days of LEA on daily integrated myofibrillar and sarcoplasmic muscle protein synthesis in young, trained females. We show that LEA impairs myofibrillar and sarcoplasmic muscle protein synthesis in trained females performing exercise training. These findings suggest that LEA may have negative consequences for skeletal muscle adaptations and highlight the importance of ensuring adequate energy availability in female athletes.

When and what to eat? A scoping review of health outcomes of fasting in conjunction with a low-carbohydrate diet.

Over the last several decades, there has been an increase in chronic diseases such as neurodegenerative, inflammatory, cardiovascular disease (CVD) and cancer. Two eating patterns, a low-carbohydrate diet (LCD) and fasting, have been researched independently over this period and found to be beneficial in reducing many of these chronic diseases' detrimental effects. However, there have been limited studies about the synergy of these eating patterns. This current scoping review aims to explore the evidence of the health outcomes of using a LCD in conjunction with fasting. Four databases were searched, and fifteen articles were found that fit the inclusion criteria. The articles reported positive effects of combining the two eating patterns for type 2 diabetes, CVD, inflammatory conditions and weight reduction and maintenance. LCD and fasting together provide synergy in decreasing metabolic syndrome (as the key causes of chronic illnesses), such as insulin levels, fasting glucose, blood pressure, TAG and regulating lipid profile. Due to the paucity of research, further high-quality studies are needed to substantiate this evidence.

Prolonged fasting outperforms short-term fasting in terms of glucose tolerance and insulin release: a randomised controlled trial.

Fasting is related to glucose intolerance and insulin resistance, but it is unknown whether the duration of fasting influences these factors. We explored whether prolonged fasting increases norepinephrine and ketone concentrations and decreases core temperature to a greater extent than short-term fasting; if so, this should lead to improved glucose tolerance. Forty-three healthy young adult males were randomly assigned to undergo a 2-d fast, 6-d fast or the usual diet. Changes in rectal temperature (TR), ketone and catecholamine concentrations, glucose tolerance and insulin release in response to an oral glucose tolerance test were assessed. Both fasting trials increased ketone concentration, and the effect was larger after the 6-d fast (P < 0·05). TR and epinephrine concentration increased only after the 2-d fast (P < 0·05). Both fasting trials increased the glucose area under the curve (AUC) (P < 0·05), but the AUC remained higher than the baseline value after participants returned to their usual diet in the 2-d fast group (P < 0·05). Neither fasting had an immediate effect on the insulin AUC, although it increased after return to their usual diet in the 6-d fast group (P < 0·05). These data suggest that the 2-d fast elicited residual impaired glucose tolerance, which may be linked to greater perceived stress during short-term fasting, as shown by the epinephrine response and change in core temperature. By contrast, prolonged fasting seemed to evoke an adaptive residual mechanism that is related to improved insulin release and maintained glucose tolerance.

Dietary intake during a pragmatic cluster-randomized weight loss trial in an underserved population in primary care.

BACKGROUND: Currently there are limited data as to whether dietary intake can be improved during pragmatic weight loss interventions in primary care in underserved individuals. METHODS: Patients with obesity were recruited into the PROPEL trial, which randomized 18 clinics to either an intensive lifestyle intervention (ILI) or usual care (UC). At baseline and months 6, 12, and 24, fruit and vegetable (F/V) intake and fat intake was determined. Outcomes were analyzed by repeated-measures linear mixed-effects multilevel models and regression models, which included random cluster (clinic) effects. Secondary analyses examined the effects of race, sex, age, and food security status. RESULTS: A total of 803 patients were recruited. 84.4% were female, 67.2% African American, 26.1% received Medicaid, and 65.5% made less than $40,000. No differences in F/V intake were seen between the ILI and UC groups at months 6, 12, or 24. The ILI group reduced percent fat at months 6, 12, and 24 compared to UC. Change in F/V intake was negatively correlated with weight change at month 6 whereas change in fat intake was positively associated with weight change at months 6, 12, and 24 for the ILI group. CONCLUSIONS: The pragmatic weight loss intervention in primary care did not increase F/V intake but did reduce fat intake in an underserved population with obesity. F/V intake was negatively associated with weight loss at month 6 whereas percent fat was positively correlated with weight loss throughout the intervention. Future efforts better targeting both increasing F/V intake and reducing fat intake may promote greater weight loss in similar populations. TRIAL REGISTRATION: NCT Registration: NCT02561221.

Beneficial effects of time and energy restriction diets on the development of experimental acute kidney injury in Rat: Bax/Bcl-2 and histopathological evaluation.

People's lifestyles and, especially, their eating habits affect their health and the functioning of the organs in their bodies, including the kidneys. One's diet influences the cells' responses to stressful conditions such as acute kidney injury (AKI). This study aims to determine the preconditioning effects of four different diets: energy restriction (ER) diet, time restriction (TR) eating, intermittent fasting (IF), and high-fat diet (HF) on histopathological indices of the kidney as well as the molecules involved in apoptosis during AKI. Adult male rats underwent ER, TR, IF, and HF diets for eight weeks. Then, AKI was induced, and renal function indices, histopathological indices, and molecules involved in apoptosis were measured. In animals with AKI, urinary albumin excretion, serum urea, creatinine and, Bax/Bcl-2 ratio increased in the kidney, while renal eGFR decreased. ER and TR diets improved renal parameters and prevented an increase in the Bax/Bcl-2 ratio. The IF diet improved renal parameters but had no effect on the Bax/Bcl-2 ratio. On the other hand, the HF diet worsened renal function and increased the Bax/Bcl-2 ratio. Histopathological examination also showed improved kidney conditions in the ER and TR groups and more damage in the HF group. This study demonstrated that ER and TR diets have renoprotective effects on AKI and possibly cause the resistance of kidney cells to damage by reducing the Bax/Bcl-2 ratio and improving apoptotic conditions.

Dietary- but not exercise-induced acute iso-energetic deficit result in short-term appetitive compensatory responses in adolescents with obesity.

BACKGROUND: Producing negative energy balance rests on the creation of energy deficits that have been shown, depending on their modality, to induce potential appetitive compensatory responses. The aim of this study was to compare energy intake (EI), appetite feelings, and the hedonic responses to equivalent acute energy deficits induced by exercise versus energy restriction in adolescents with obesity. METHODS: In a within-participants design, seventeen adolescents with obesity (12-16 years, Tanner stage 3-5, 9 males) randomly completed three conditions: i) control (CON); ii) deficit induced by diet only (Def-EI); and iii) deficit induced by exercise only (Def-EX). Lunch was calibrated to generate a 400-kcal deficit in Def-EI and remained similar in CON and Def-EX. A 400-kcal deficit was created through a cycling bout set at 65% VO2peak in Def-EX. Ad libitum EI, macronutrient intake and relative EI (REI) were assessed at dinner, subjective appetite sensations taken at regular intervals, and food reward measured before dinner. RESULTS: Food intake at dinner was greater in Def-EI (1112 ± 265 kcal) compared to CON (983 ± 277 kcal; p = 0.005) and Def-EX (1009 ± 281 kcal; p = 0.025). Absolute protein and lipid intake were significantly higher in Def-EI (52.4 ± 9.5 g and 36.8 ± 8.9 g respectively) compared with both CON (44.9 ± 12.6 g; p = 0.001 and 33.8 ± 10.1 g; p = 0.002 respectively) and Def-EX (47.3 ± 11.8 g, p = 0.018, 35.4 ± 10.1 g, p = 0.036 respectively). Area under the curve (AUC) for hunger, desire to eat and prospective food consumption were significantly higher in Def-EI compared with both CON (p = 0.0001) and Def-EX (p = 0.0001). AUC for fullness was significantly lower on Def-EI compared with CON and Def-EX (p = 0.0001). Implicit wanting for sweet food was significantly lower on Def-EX (p = 0.031), relative to CON. CONCLUSION: Appetitive compensatory responses that are observed after iso-caloric energy restriction in adolescents with obesity are absent with acute exercise, which could contribute to optimize our impact on short-term energy balance.

The effects of empagliflozin, dietary energy restriction, or both on appetite-regulatory gut peptides in individuals with type 2 diabetes and overweight or obesity: The SEESAW randomized, double-blind, placebo-controlled trial.

AIM: To assess the impact of the sodium-glucose co-transporter-2 (SGLT2) inhibitor empagliflozin (25 mg once-daily), dietary energy restriction, or both combined, on circulating appetite-regulatory peptides in people with type 2 diabetes (T2D) and overweight or obesity. MATERIALS AND METHODS: In a double-blind, placebo-controlled trial, 68 adults (aged 30-75 years) with T2D (drug naïve or on metformin monotherapy; HbA1c 6.0%-10.0% [42-86 mmol/mol]) and body mass index of 25 kg/m2 or higher were randomized to (a) placebo only, (b) placebo plus diet, (c) empagliflozin only or (d) empagliflozin plus diet for 24 weeks. Dietary energy restriction matched the estimated energy deficit elicited by SGLT2 inhibitor therapy through urinary glucose excretion (~360 kcal/day). The primary outcome was change in postprandial circulating total peptide-YY (PYY) during a 3-hour mixed-meal tolerance test from baseline to 24 weeks. Postprandial total glucagon-like peptide-1 (GLP-1), acylated ghrelin and subjective appetite perceptions formed secondary outcomes, along with other key components of energy balance. RESULTS: The mean weight loss in each group at 24 weeks was 0.44, 1.91, 2.22 and 5.74 kg, respectively. The change from baseline to 24 weeks in postprandial total PYY was similar between experimental groups and placebo only (mean difference [95% CI]: -8.6 [-28.6 to 11.4], 13.4 [-6.1 to 33.0] and 1.0 [-18.0 to 19.9] pg/ml in placebo-plus diet, empagliflozin-only and empagliflozin-plus-diet groups, respectively [all P ≥ .18]). Similarly, there was no consistent pattern of difference between groups for postprandial total GLP-1, acylated ghrelin and subjective appetite perceptions. CONCLUSIONS: In people with T2D and overweight or obesity, changes in postprandial appetite-regulatory gut peptides may not underpin the less than predicted weight loss observed with empagliflozin therapy. CLINICAL TRIALS REGISTRATION: NCT02798744, www. CLINICALTRIALS: gov; 2015-001594-40, www.EudraCT.ema.europa.eu; ISRCTN82062639, www.ISRCTN.org.

Intermittent fasting and continuous energy restriction result in similar changes in body composition and muscle strength when combined with a 12 week resistance training program.

PURPOSE: The objective of this study was to compare the effects of 12 weeks of resistance training combined with either 5:2 intermittent fasting or continuous energy restriction on body composition, muscle size and quality, and upper and lower body strength. METHODS: Untrained individuals undertook 12 weeks of resistance training plus either continuous energy restriction [20% daily energy restriction (CERT)] or 5:2 intermittent fasting [~ 70% energy restriction 2 days/week, euenergetic consumption 5 days/week (IFT)], with both groups prescribed a mean of ≥ 1.4 g of protein per kilogram of body weight per day. Participants completed 2 supervised resistance and 1 unsupervised aerobic/resistance training combination session per week. Changes in lean body mass (LBM), thigh muscle size and quality, strength and dietary intake were assessed. RESULTS: Thirty-four participants completed the study (CERT = 17, IFT = 17). LBM was significantly increased (+ 3.7%, p < 0.001) and body weight (- 4.6%, p < 0.001) and fat (- 24.1%, p < 0.001) were significantly reduced with no significant difference between groups, though results differed by sex. Both groups showed improvements in thigh muscle size and quality, and reduced intramuscular and subcutaneous fat assessed by ultrasonography and peripheral quantitative computed tomography (pQCT), respectively. The CERT group demonstrated a significant increase in muscle surface area assessed by pQCT compared to the IFT group. Similar gains in upper and lower body strength and muscular endurance were observed between groups. CONCLUSION: When combined with resistance training and moderate protein intake, continuous energy restriction and 5:2 intermittent fasting resulted in similar improvements in body composition, muscle quality, and strength. ACTRN: ACTRN12620000920998, September 2020, retrospectively registered.

A Comparative Study of the Anti-Obesity Effects of Dietary Sea Cucumber Saponins and Energy Restriction in Response to Weight Loss and Weight Regain in Mice.

Dietary supplementation of sea cucumber saponins and calorie restriction have been proved to be effective in alleviating obesity, but the differences of anti-obesity effects between sea cucumber saponins and energy restriction during weight loss and weight regain are still unknown. In the present study, high-fat-induced obesity mice were randomly divided into three groups, including a high-fat diet group (HF), an energy restriction by 40% group (HF-L), and a sea cucumber saponins group (HF-S), to compare the effects of dietary sea cucumber saponins and energy restriction on the weight, glucose, and lipid metabolism of obese mice during weight loss and weight regain. The results showed that dietary 0.06% sea cucumber saponins and limiting energy intake by 40% had the same weight loss effect. Interestingly, sea cucumber saponins could alleviate impaired glucose tolerance and insulin resistance caused by obesity. In addition, the inhibited SREBP-1c mediated lipogenesis might lead to the alleviation of weight regain after resuming the high-fat diet even when sea cucumber saponins were no longer supplemented. In contrast, limiting energy intake tended to promote lipid synthesis in the liver and white adipose tissue after restoring a high-fat diet, and inflammation was also induced. The findings indicated that sea cucumber saponins could replace calorie restriction to prevent obesity and might be used as a functional food or drug to resist obesity and related diseases caused by obesity.

Comparative genomics of in vitro and in vivo evolution of probiotics reveals energy restriction not the main evolution driving force in short term.

Probiotics have attracted much attention because of their health-promoting effects, but little is known about the in vivo evolution of probiotics. This study analyzed the genome adaptation of the probiotic Lactiplantibacillus plantarum P-8 strain cultivated in ordinary and glucose restrictive growth media. Then, this study re-analyzed genomes of P-8 isolates recovered from the gut contents of subjects in two feeding trials (in rat and human). The sampling time points were similar to that of the in vitro evolution experiment, which might give parallel comparison of the in vitro and in vivo evolution processes. Our results showed that intra-individual specific microbial genomic variants of the original strain were detected in all human and some rat subjects. The divergent patterns of evolution within the host gastrointestinal tract suggested intra-individual-specific environmental adaptation. Based on comprehensive analysis of adapted-isolates recovered from these experiments, our results showed that the energy restriction was not the main driving force for evolution of probiotics. The individual-specific adaptation of probiotics might partially explain the varying extent of health effects seen between different individuals after probiotic consumption. In addition, the results suggest that probiotics should not only adapt to the environment of the birth canal, but also adapt to other species in the gut, revealing the Red Queen hypothesis in the process of intestinal flora.

Mass Spectrometric Metabolic Fingerprinting of 2-Deoxy-D-Glucose (2-DG)-Induced Inhibition of Glycolysis and Comparative Analysis of Methionine Restriction versus Glucose Restriction under Perfusion Culture in the Murine L929 Model System.

All forms of restriction, from caloric to amino acid to glucose restriction, have been established in recent years as therapeutic options for various diseases, including cancer. However, usually there is no direct comparison between the different restriction forms. Additionally, many cell culture experiments take place under static conditions. In this work, we used a closed perfusion culture in murine L929 cells over a period of 7 days to compare methionine restriction (MetR) and glucose restriction (LowCarb) in the same system and analysed the metabolome by liquid chromatography mass spectrometry (LC-MS). In addition, we analysed the inhibition of glycolysis by 2-deoxy-D-glucose (2-DG) over a period of 72 h. 2-DG induced very fast a low-energy situation by a reduced glycolysis metabolite flow rate resulting in pyruvate, lactate, and ATP depletion. Under perfusion culture, both MetR and LowCarb were established on the metabolic level. Interestingly, over the period of 7 days, the metabolome of MetR and LowCarb showed more similarities than differences. This leads to the conclusion that the conditioned medium, in addition to the different restriction forms, substantially reprogramm the cells on the metabolic level.

Diet Quality following Total Meal Replacement Compared with Food-Based Weight-Loss Diets in Postmenopausal Women with Obesity: A Secondary Analysis of the TEMPO Diet Trial.

BACKGROUND: Severely energy-restricted diets that utilize meal-replacement products are the most effective dietary treatment for obesity. However, there are concerns they may fail to educate individuals on how to adopt a healthy food-based diet after weight loss. OBJECTIVES: The aim of this research was to compare changes in diet quality following total meal replacement compared with food-based weight-loss diets. METHODS: In this secondary analysis of a randomized controlled trial, 79 postmenopausal women aged 45-65 y, with a BMI (in kg/m2) of 30-40, were randomly assigned to either a total meal-replacement diet (energy intake restricted by 65-75% relative to requirements) for 16 wks, followed by a food-based diet (energy intake restricted by 25-35% relative to requirements) until 52 wks, or the food-based diet for the entire 52-wk period. Diet quality was scored at baseline and 52 wks using the Healthy Eating Index for Australian Adults, with score changes compared between groups using an independent t test. RESULTS: Diet quality improved from baseline in both groups, but less so in the total meal-replacement group, with a mean (SD) increase of 3.6 (10.8) points compared with 11.8 (13.9) points in the food-based group, resulting in a mean between-group difference of -8.2 (P = 0.004; 95% CI: -13.8, -2.7) points. This improvement in diet quality within both groups was mostly driven by a reduction in the intake of discretionary foods. Intake remained below the recommendations at 52 wks for 4 of the 5 food groups in both dietary interventions. CONCLUSIONS: In postmenopausal women with obesity, weight-loss interventions that involve either a total meal-replacement diet or a food-based diet both improve diet quality, however, not sufficiently to meet recommendations. This highlights the importance of addressing diet quality as a part of all dietary weight-loss interventions. This trial is registered with the Australia and New Zealand Clinical Trials Registry as 12612000651886.

Impact of intermittent energy restriction on anthropometric outcomes and intermediate disease markers in patients with overweight and obesity: systematic review and meta-analyses.

This systematic review aims to investigate the effects of intermittent energy restriction (IER) on anthropometric outcomes and intermediate disease markers. A systematic literature search was conducted in three electronic databases. Randomized controlled trials (RCTs) were included if the intervention lasted ≥12 weeks and IER was compared with either continuous energy restriction (CER) or a usual diet. Random-effects meta-analysis was performed for eight outcomes. Certainty of evidence was assessed using GRADE. Seventeen RCTs with 1328 participants were included. IER in comparison to a usual diet may reduce body weight (mean difference [MD]: -4.83 kg, 95%-CI: -5.46, -4.21; n = 6 RCTs), waist circumference (MD: -1.73 cm, 95%-CI: -3.69, 0.24; n = 2), fat mass (MD: -2.54 kg, 95%-CI: -3.78, -1.31; n = 6), triacylglycerols (MD: -0.20 mmol/L, 95%-CI: -0.38, -0.03; n = 5) and systolic blood pressure (MD: -6.11 mmHg, 95%-CI: -9.59, -2.64; n = 5). No effects were observed for LDL-cholesterol, fasting glucose, and glycosylated-hemoglobin. Both, IER and CER have similar effect on body weight (MD: -0.55 kg, 95%-CI: -1.01, -0.09; n = 13), and fat mass (MD: -0.66 kg, 95%-CI: -1.14, -0.19; n = 10), and all other outcomes. In conclusion, IER improves anthropometric outcomes and intermediate disease markers when compared to a usual diet. The effects of IER on weight loss are similar to weight loss achieved by CER.