Effects Of Energy Restriction Research Articles

Energy restriction inhibits β-catenin ubiquitination to improve ischemic stroke injury via USP18/SKP2 axis.

Ischemic stroke (IS) remains a global health issue because of its great disability and mortality. Energy restriction (ER) has been justified to perform an inhibitory role in cerebral injury caused by IS. This research was purposed to inquire the potential molecular mechanism of ER in IS. To verify the function of ER in the animal and cell models of IS, rats were subjected to intermittent fasting (IF) and middle cerebral artery occlusion/reperfusion (MCAO/R) surgery and HAPI cells were treated with oxygen-glucose deprivation and reoxygenation (OGD/R) and 2-deoxyglucose (2-DG). It was disclosed that IF mitigated brain damage and inflammation in MCAO/R rats. Likewise, ER inhibited OGD/R-evoked microglial activation and inflammatory response. Of note, ubiquitin specific protease 18 (USP18) was uncovered to be the most significantly upregulated in MCAO/R rats receiving IF compared to free-feeding MCAO/R rats. Real-time quantitative polymerase chain reaction (RT-qPCR) and western blot verified that ER led to the promotion of USP18 expression. Moreover, downregulation of USP18 neutralized the meliorative effects of ER on OGD/R-treated HAPI cells. Functionally, USP18 restrained β-catenin ubiquitination to enhance its expression. In addition, our results manifested that S-phase kinase associated protein 2 (SKP2) contributed to degradation of β-catenin and USP18 abolished the role of SKP2 in β-catenin ubiquitination. Knockout of USP18 eliminated the protective effects of IF on MCAO/R rats, while SKP2 exacerbated brain damage and inflammation by decreasing β-catenin expression after IF. In summary, we validated that ER-induced USP18 exerts a suppressive function in IS damage through SKP2-mediated β-catenin ubiquitination.

Replacement of dietary carbohydrate with protein increases fat mass and reduces hepatic triglyceride synthesis and content in female obese Zucker rats.

Previous studies have demonstrated both energy restriction (ER) and higher protein (HP), lower carbohydrate (LC) diets downregulate hepatic de novo lipogenesis. Little is known about the independent and combined impact of ER and HP/LC diets on tissue-specific lipid kinetics in leptin receptor-deficient, obese rodents. This study investigated the effects of ER and dietary macronutrient content on body composition; hepatic, subcutaneous adipose tissue (SAT), and visceral AT (VAT) lipid metabolic flux (2 H2 O-labeling); and blood and liver measures of cardiometabolic health in six-week-old female obese Zucker rats (Leprfa+/fa+ ). Animals were randomized to a 10-week feeding intervention: adlibitum (AL)-HC/LP (76% carbohydrate/15% protein), AL-HP/LC (35% protein/56% carbohydrate), ER-HC/LP, or ER-HP/LC. ER groups consumed 60% of the feed consumed by AL. AL gained more fat mass than ER (P-energy = 0.012) and HP/LC gained more fat mass than HC/LP (P-diet = 0.025). Hepatic triglyceride (TG) concentrations (P-interaction = 0.0091) and absolute hepatic TG synthesis (P-interaction = 0.012) were lower in ER-HP/LC versus ER-HC/LP. ER had increased hepatic, SAT, and VAT de novo cholesterol fractional synthesis, absolute hepatic cholesterol synthesis, and serum cholesterol (P-energy≤0.0035). A HP/LC diet, independent of energy intake, led to greater gains in fat mass. A HP/LC diet, in the context of ER, led to reductions in absolute hepatic TG synthesis and TG content. However, ER worsened cholesterol metabolism. Increased adipose tissue TG retention with the HP/LC diet may reflect improved lipid storage capacity and be beneficial in this genetic model of obesity.

FRI005 Appetite Response To Short-term Energy Restriction In Young Healthy Women

Abstract Disclosure: G.E. Choi: None. C. Okigbo: None. J. Tessa Tonleu: None. S. Shekhar: None. H.F. Leka: None. A.E. Kim: None. B. Purse: None. K.R. Hisch: None. A.E. Smith-Ryan: None. J.E. Hall: None. Short-term caloric restriction, also referred to as energy restriction (ER), is commonly used by women across the weight spectrum to address their weight or health. Chronic ER is associated with increased appetite, but the relationship is poorly characterized in short-term ER or in the absence of obesity. We investigated the impact of controlled short-term ER on appetite and relevant hormone mediators in young women. In the early follicular phase of two menstrual cycles, 19 healthy non-obese women aged 23.36 ± 2.08 years (mean ± SD) with a BMI of 23.15 ± 2.34 kg/m2 (mean ± sem) underwent two five-day diet and exercise interventions: neutral energy availability (NEA) = 45 kcal/kg lean body mass (LBM)/day and deficient energy availability (DEA) = 20 kcal/kg LBM/day. On day 5 of both interventions, a visual analog scale (VAS) appetite questionnaire, body weight, fasting leptin and orexin-A were measured. We used paired t-tests for comparisons of changes from NEA to DEA. Principal-component factor analysis divided VAS items into appetite, satiety, and hunger (Cronbach alphas >0.80). We utilized linear regression models to determine how changes (Δ) in body weight, leptin, and orexin-A affect appetite, satiety, hunger, and cravings. From NEA to DEA, appetite and hunger increased (55% vs 76%; p<0.001 and 52% vs 71%; p<0.001, respectively), while satiety and cravings decreased (42% vs 19%; p <0.01 and 49% to 38%; p<0.01, respectively). DEA resulted in a weight loss of 1.0±0.22 kg (p<0.001), a decrease in leptin of 3.13±0.95 ng/ml, p=0.002), and increased orexin-A (0.06±0.02 ng/ml, p=0.018). Δ body weight was positively associated with Δ leptin (p=0.001) but not Δ orexin-A. When adjusting for leptin and orexin-A, increased appetite was associated with weight loss (p=0.011). Δ satiety was independently correlated with Δ body weight (p=0.002) and Δ leptin (p=0.033). Δ hunger was positively correlated with Δ body weight (p=0.043), independent of Δ orexin-A). Δ leptin, orexin-A, or body weight did not correlate with Δ craving. Thus, even in non-obese women, short-term ER results in a profound effect on homeostatic mechanisms designed to maintain weight; increased appetite and decreased satiety are mediated by even a minor degree of weight loss, both independently and through decreased leptin. It is likely that changes in ghrelin also contribute to these adaptations to ER, however it was not measured in this study for technical reasons. Interestingly, the effect of short-term ER on specific food cravings is overwhelmed by the overall increase in appetite. Presentation: Friday, June 16, 2023

Effects of energy restriction during growing phase on the productive performance of Hyline Brown laying hens aged 6 to 72 wk

The aim of this study was to assess the effects of energy-restricted feeding during growing phase on the productive performance of Hyline Brown laying hens aged 6 to 72 wk. A total of 720 six-week-old layer chicks were allocated equally to 3 groups with 6 replicates of 40 pullets each, and were fed 1 of 3 diets that were nutritionally similar except for the apparent metabolizable energy corrected for nitrogen (AMEn) content. At the age of 6 to 17 wk, the pullets in the control group were given diet with 2,850 kcal/kg AMEn, and were fed ad libitum. The levels of AMEn in diet of pullets in the experimental groups were 90% (2,565 [2,850×90%] kcal/kg) and 80% (2,280 [2,850×80%] kcal/kg) of that in control group, and the daily amount of feed was restricted to the absolute quantity of the diet consumed by pullets in control group. At the age of 18 to 72 wk, all the hens were fed with the same diets ad libitum. As energy restriction increased in the growing phase, body weight (BW) dropped at the ages of 12 and 15 to 23 wk (at 23 wk: P=0.001; at other ages: P < 0.001), but it showed no significant difference at 24 wk (P=0.071). At 20 wk, restricting energy induced a delay in the development of sexual organs, including the ovary stroma, oviduct, and small yellow follicle (P < 0.05), as well as a delay in sexual maturity (P < 0.05). Consequently, the laying rate in the first and second periods dropped linearly (P=0.046, 0.030, and 0.038, P < 0.001, respectively). The coefficient of variation (CV) in the BW at 19, 20, and 21 wk (P=0.040, 0.023, and 0.042, respectively), the CV of age at first egg (P < 0.001), and CV of individual egg number at age 18 to 72 wk (P < 0.001) decreased linearly. There was a linear increase in the laying rate of hens in the later periods (at age 32-72 wk, P < 0.05), as well as in the average total egg number per hen and average laying rate at the age of 18 to 72 wk (P=0.006). The average egg mass also showed a linear increase with increasing levels of energy restriction (P < 0.001). In summary, although appropriate energy restriction during growing phase delayed sexual maturity and sexual organ development in early-laying Hyline Brown pullets, it improved uniformity of BW, age at first egg laying, and individual egg number, and increased egg number per hen, laying rate, average egg mass, and number of settable eggs from 18 to 72 wk of age.

Effect of Energy Restriction on Malondialdehyde Levels in Rats

Elevated malondialdehyde (MDA) levels indicate the occurrence of cell membrane oxidation. Calorie restriction is known to extend life expectancy. This study aims to investigate the effect of calorie restriction on MDA levels in young and old rats. An experimental approach was employed using Rattus norvegicus Wistar strain as the experimental animals, with a pre-post-test control group design. A total of 28 white rats were included in this study and were divided into four groups. The control groups, Group A and Group B, received standard feed and unrestricted access to distilled water, while the treatment groups, Group C and Group D, were fed with a 40% reduction in calorie intake and distilled water. Data analysis was performed using SPSS 21.0 (SPSS, Inc., Chicago, IL) with a 0.05 significance level. The results showed a difference in MDA level changes between group B (control group) and group D (treatment group) (p&lt;0.05). This study concludes that MDA levels are higher in the elderly compared to young rats, and a 40% calorie restriction can reduce MDA levels.

Effects of energy restriction and exercise on pain and inflammation in patients with knee osteoarthritis

Effects of energy restriction and exercise on pain and inflammation in patients with knee osteoarthritis

Effects of energy restriction with and without almonds on weight and cardiometabolic risk factors

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1462-P: Effect of Energy Restriction on the Intracellular Metabolism of Rodent Pancreatic ß-Cells In Vitro and Obese Mice

Background: In pancreatic β-cells under diabetic conditions, metabolic stressors cause mitochondrial dysfunction and reduce oxidative phosphorylation, resulting in impaired intracellular metabolism. It has been suggested that aberrant activation of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) plays a role in this impairment. However, it is not clear whether the defect in activation of PFKFB3 is reversible. We investigated the effects of energy restriction on PFKFB3 and other metabolic enzymes in pancreatic β-cells. Methods: INS-1 832/13 cells and islets from C57BL/6J mice were cultured in medium containing a low (5.5 mM; low-G) or a high (22 mM: high-G) glucose concentration for 48 hours, or high-G for 24 hours followed by low-G for another 24 hours. The protein expression of glycolysis-related enzymes was measured using western blotting (WB) . Next, 6-week-old ob/+ and ob/ob mice were fed a standard chow diet ad lib or the same diet restricted to 2 g/day for 4 weeks. The body mass, blood glucose concentration, glucose tolerance, and insulin resistance of the mice were compared. The expression of glycolytic enzymes in the pancreatic islets was evaluated using WB and immunohistochemical staining. Results: In both INS-1 832/13 cells and isolated islets, higher expression of PKFFB3 was observed in the high-G group than in the low-G group. However, this was normalized by changing from a high-G to a low-G environment. Ad lib-fed ob/ob mice showed hyperglycemia and greater weight gain than ob/+ mice. The expression of PFKFB3, isocitrate dehydrogenase, and hexokinase was higher in ad lib-fed ob/ob mice. Restricted feeding suppressed weight gain and improved glucose tolerance versus ad lib-fed ob/ob mice. The high expression of PFKFB3 was ameliorated by restricted feeding. Conclusion: The intracellular metabolic changes in pancreatic β cells that are associated with obesity and diabetes are flexible. Disclosure K. Chiba: Research Support; Grant for Young Researcher from Japan Association for Diabetes Education and Care, Japan Diabetes Society Junior Scientist Development Grant, Japan Society for the Promotion of Science, MSD Life Science Foundation, Promotion for Young Research Talent and Network, The Akiyama Life Science Foundation, The Uehara Memorial Foundation. H. Nomoto: None. R. Izumihara: None. H. Kameda: None. K. Cho: None. H. Miyoshi: Research Support; Abbott Japan Co., Ltd., Boehringer Ingelheim International GmbH, Daiichi Sankyo, Kowa Company, Ltd., LifeScan, Mitsubishi Tanabe Pharma Corporation, Novo Nordisk, Ono Pharmaceutical Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Holdings Co., Ltd. Speaker's Bureau; Astellas Pharma Inc., Boehringer Ingelheim International GmbH, Eli Lilly and Company, Kowa Company, Ltd., Merck &amp; Co., Inc., Mitsubishi Tanabe Pharma Corporation, Novo Nordisk, Ono Pharmaceutical Co., Ltd., Sanofi K.K., Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Holdings Co., Ltd. T. Atsumi: Consultant; AbbVie Inc., AstraZeneca, MEDICAL &amp; BIOLOGICAL LABORATORIES CO., Nippon Boehringer Ingelheim Co. Ltd., Novartis Pharma K.K., Ono Pharmaceutical Co., Ltd., Pfizer Inc. Research Support; AbbVie Inc., Alexion Pharmaceuticals, Inc., Astellas Pharma Inc., Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo, Mitsubishi Tanabe Pharma Corporation, Nippon Boehringer Ingelheim Co. Ltd., Otsuka Pharmaceutical Co., Ltd., Pfizer Inc., Taiho Pharmaceutical Co. Ltd., Takeda Pharmaceutical Company Limited, Teijin Pharma Limited. Speaker's Bureau; AbbVie Inc., Astellas Pharma Inc., Bristol-Myers Squibb Company, Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo, Eisai Co., Ltd., Eli Lilly and Company, Kyowa Kirin Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Novartis Pharma K.K., Pfizer Inc., Taiho Pharmaceutical Co. Ltd., Takeda Pharmaceutical Company Limited, UCB, Inc.

Melatonin alleviated oxidative stress induced by energy restriction on sheep Leydig cells through Sirt1/Sod2 pathway

Energy balance is essential for normal reproduction of ram. However, the effect of energy restriction (ER) on reactive oxygen species (ROS) of sheep Leydig cells (LCs) and the rescuee methods are still unclear. To investigate the in vitro effect of melatonin on cellular ROS in fER-treated sheep LCs and explore the underlying mechanism, Hu sheep LCs were restricted energy using no serum culture medium and resaved with 10 ng/ml melatonin, respectively. The results showed that ER significantly increased MDA level, while decreased CAT, GHS-px expression and ΔΨm (p < 0.05). Meanwhile, ER decreased testosterone concentration and cell proliferation rate (p < 0.05). And the expression of testosterone synthesis-related enzymes was also down-regulated by ER (p < 0.05). Furthermore, we revealed that melatonin reversed the defective phenotypes in ER-treated LCs via Sirt1/Sod2 pathway. The interference of Sirt1 abolished the melatonin-mediated improvement of cellular ROS and testosterone secretion. Taken together, our study firstly indicated that melatonin could alleviate the excessive ROS accumulation and promote testosterone biosynthesis in ER-treated sheep LCs via the activation of Sirt1/Sod2 pathway.

The Effects of Energy Restriction on Thyroid Hormone Dynamics

Abstract Background: Intermittent energy restriction (IER) is gaining popularity as a weight-loss strategy. However, the effect of short-term energy restriction on thyroid hormone dynamics is not well characterized. Methods: Nineteen healthy women age 23.36± 2.08 yr (mean ± SD) with normal baseline thyroid function and negative anti-thyroid antibodies underwent two 5-day interventions of a prescribed diet and identical standardized exercise in the early follicular phase of two menstrual cycles - neutral energy availability (NEA) 45 kCal/kg*LBM/d followed by deficient energy availability (DEA) 20 kCal/kg*LBM/d. Energy requirements were estimated as previously described (doi.org/10.1210/jendso/bvaa046.1468) and were used to generate a diet and exercise regimen for each participant. On day 5 of both interventions, body composition was assessed by BodPod®. Standardized NEA or DEA breakfast and lunch were provided as appropriate as well as a standardized NEA snack on both sampling visits. Blood sampling was performed for 8 hours starting at ~0800 h with measurement of TSH and growth hormone (GH) every 10 min, cortisol every 30 min, total T3 (TT3), reverse T3 (rT3) and total T4 (TT4) every 60 min, free T3 (FT3), free T4 (FT4) and TBG at the beginning and end of sampling. Liquid chromatography-tandem mass spectrometry (LC-MS) was used for measurements of all thyroid hormones, with the exception of TSH and TBG which were measured by ELISA as were GH and cortisol. Data were analyzed using ANOVA-RM and linear mixed models. Results are presented as mean or least squared mean ± sem. Results: Body mass index, bodyweight and % fat mass were not different between interventions. GH and cortisol were unaffected by DEA (p=0.46, p=0.63). TBG was not affected by time of day or dietary intervention (p=0.95, p=0.41). However, compared with NEA, TT3 (89.15 ± 2.89 vs 95.55 ± 2.89 ng/dL for DEA and NEA, respectively; p&amp;lt;0.0001) and TSH (0.92 ± 0.08 vs 1.03 ± 0.09 μIU/mL; p=0.0011) were lower after DEA, while TT4 (6.26 ± 0.25 vs 6.06 ± 0.25 μg/dL; p=0.04), FT4 (3.37 ± 0.26 vs 2.94 ± 0.25 ng/d;, p=0.0052) and rT3 (11.77 ± 0.58 vs 8.85 ± 0.51 ng/dL; p&amp;lt;0.0001) were higher. Regardless of dietary intervention, FT3 (p=0.0005), TT3 (p&amp;lt;0.0001), TT4 (p&amp;lt;0.0001) and TSH (p&amp;lt;0.0001) decreased across the day. Conclusion: Using LC-MS for as a more robust measure of thyroid hormones, we have now shown that changes in thyroid hormone dynamics occur after only 5 days of 55% energy restriction in the absence of alterations in body composition, cortisol, GH, TBG or the circadian pattern of thyroid hormone secretion. The decrease in TSH combined with the decrease in TT3 and increase in rT3 support the contribution of both central and peripheral mechanisms to these changes. Taken together these results provide support for a multi-level adaptation in thyroid hormone dynamics to conserve energy expenditure in response to short-term energy restriction.

Increased 1,25(OH)2-Vitamin D Concentrations after Energy Restriction Are Associated with Changes in Skeletal Muscle Phenotype.

The influence of energy restriction (ER) on muscle is controversial, and the mechanisms are not well understood. To study the effect of ER on skeletal muscle phenotype and the influence of vitamin D, rats (n = 34) were fed a control diet or an ER diet. Muscle mass, muscle somatic index (MSI), fiber-type composition, fiber size, and metabolic activity were studied in tibialis cranialis (TC) and soleus (SOL) muscles. Plasma vitamin D metabolites and renal expression of enzymes involved in vitamin D metabolism were measured. In the ER group, muscle weight was unchanged in TC and decreased by 12% in SOL, but MSI increased in both muscles (p < 0.0001) by 55% and 36%, respectively. Histomorphometric studies showed 14% increase in the percentage of type IIA fibers and 13% reduction in type IIX fibers in TC of ER rats. Decreased size of type I fibers and reduced oxidative activity was identified in SOL of ER rats. An increase in plasma 1,25(OH)2-vitamin D (169.7 ± 6.8 vs. 85.4 ± 11.5 pg/mL, p < 0.0001) with kidney up-regulation of CYP27b1 and down-regulation of CYP24a1 was observed in ER rats. Plasma vitamin D correlated with MSI in both muscles (p < 0.001), with the percentages of type IIA and type IIX fibers in TC and with the oxidative profile in SOL. In conclusion, ER preserves skeletal muscle mass, improves contractile phenotype in phasic muscles (TC), and reduces energy expenditure in antigravity muscles (SOL). These beneficial effects are closely related to the increases in vitamin D secondary to ER.

The effect of energy restriction on development and progression of chronic kidney disease: review of the current evidence.

Energy restriction (ER) has anti-ageing effects and probably protects from a range of chronic diseases including cancer, diabetes and chronic kidney disease (CKD). Specifically, ER has a positive impact on experimental kidney ageing, CKD (diabetic nephropathy, polycystic kidney disease) and acute kidney injury (nephrotoxic, ischaemia-reperfusion injury) through such mechanisms as increased autophagy, mitochondrial biogenesis and DNA repair, and decreased inflammation and oxidative stress. Key molecules contributing to ER-mediated kidney protection include adenosine monophosphate-activated protein kinase, sirtuin-1 and PPAR-γ coactivator 1α. However, CKD is a complex condition, and ER may potentially worsen CKD complications such as protein-energy wasting, bone-mineral disorders and impaired wound healing. ER mimetics are drugs, such as metformin and Na-glucose co-transporter-2 which mimic the action of ER. This review aims to provide comprehensive data regarding the effect of ER on CKD progression and outcomes.

Impact of physical activity and energy restriction on immune regulation of cancer.

Cancer is a major public health issue worldwide. Lifestyle factors, such as body weight and physical activity (PA), significantly impact cancer risk and progression. There is strong evidence that PA reduces and obesity increases risk and mortality from numerous cancer types. Energy restriction (ER) in non-obese hosts significantly reduces tumor incidence in a variety of preclinical models, and reduces body weight and cardiometabolic risk factors in humans. Emerging data suggest that PA- and ER-induced changes in inflammatory and immune mediators may contribute to the cancer prevention effects of these interventions. A systematic literature search was conducted to identify studies that evaluated the impact of PA and ER on tumor and immune outcomes in humans and animal models. A total of 97 eligible studies were identified (68 studies reporting PA interventions and 30 studies reporting ER interventions). Thirty-one studies investigated the effect of PA on cancer immune outcomes using preclinical cancer models of breast (n=17, 55%), gastrointestinal (n=6, 19%), melanoma (n=4, 13%), and several other cancer types (n=4, 13%). Despite the heterogeneity in study designs, the majority of studies (n=23, 74%) reported positive effects of PA on tumor outcomes. Thirty-seven clinical studies investigated the effect of PA on cancer immune outcomes. None reported tumor outcomes, thus only immune outcomes were evaluated in these studies. PA studies were conducted in patients with breast (n=22, 59%), gastrointestinal (n=5, 14%), prostate (n=2, 5%), esophageal (n=1, 3%), lung (n=1, 3%) cancer, leukemia (n=1, 3%), or mixed cancer types (n=5, 14%). Twenty-two studies investigated the effect of ER interventions on cancer immune outcomes using preclinical cancer models including breast (n=5, 23%), gastrointestinal (n=5, 23%), lung (n=2, 9%), liver (n=2, 9%), pancreatic (n=2, 9%), and several other cancer types (n=6, 27%). Positive effects of ER on tumor outcomes were reported in 21 of 22 studies. Six clinical studies investigated the effect of ER (in combination with PA) on tumor immune outcomes in cancer patients with overweight or obesity. Five were conducted in breast cancer patients, and one recruited patients of a mix of cancer types. A wide range of immunological parameters including immune cell phenotype and function, cytokines, and other immune and inflammatory markers were assessed in multiple tissue compartments (blood, spleen, lymph nodes and tumor) in the included studies. Results from preclinical and clinical studies suggest that both PA and ER exert heterogeneous effects on circulating factors and systemic immune responses. PA + ER alters the gene expression profile and immune infiltrates in the tumor which may result in a reduction in immune suppressive factors. However, additional studies are needed to better understand the effect of PA and/or ER on immunomodulation, particularly in the tumor microenvironment (TME).

Effects of Prolonged Energy Restriction and Dietary Protein on Muscle Protein Synthesis and Proteome Dynamics in Obese Zucker Rats

Abstract Objectives High protein (HP) diets during short-term energy restriction (ER) attenuate energy-mediated reductions in muscle protein synthesis (MPS). MPS-adaptive responses to HP diets during prolonged ER are not well described. This study examined the effects of prolonged ER and HP on MPS and the synthesis rates of numerous individual muscle proteins. Methods Female 6-wk-old obese Zucker (leprfa+/fa+, n = 48) rats were randomized to one of four diet groups for 10 weeks: ad libitum-standard protein (AL-SP; 14% protein), AL-HP (35% protein), ER-SP, and ER-HP (both fed 60% of intake of AL-SP). At the start of week 10, D2O was administered by intraperitoneal injection and isotopic equilibrium was maintained daily by providing D2O in drinking water. Rats were euthanized after 1 week of labeling, and mixed-MPS (gastrocnemius), absolute mixed-MPS (mixed-MPS x muscle protein content), proteome dynamics, and protein half-lives [rate/d (k) = –ln(1-f)/d, where f is mixed-MPS and t is time in days; t1/2 (days) = ln(2)/k] were quantified. Results Mixed-MPS was not altered by energy status and protein intake. Gastrocnemius mass was lower (P &amp;lt; 0.001) in ER-fed rats than AL-fed rats and higher (P = 0.034) for AL-HP than AL-SP. As a result, absolute mixed-MPS was lower (P &amp;lt; 0.005) in ER than AL, regardless of dietary protein. Absolute synthesis in 24 of 26 myofibrillar, 32 of 61 mitochondrial, and 55 of 60 cytoplasmic measured proteins were lower in ER than AL (P &amp;lt; 0.05), regardless of dietary protein. The difference in absolute synthesis of myofibrillar, mitochondrial, and cytoplasmic proteins due to ER compared to AL was 28%, 16%, and 27%, respectively. Comparison of HP and SP within each energy state revealed lower turnover rates and prolonged half-lives for a majority of measured muscle proteins in HP than in SP in both ER and AL conditions (P &amp;lt; 0.001). Conclusions Prolonged ER in obese Zucker rats exerted a strong suppressive effect on myofibrillar, mitochondrial, and cytoplasmic MPS, suggesting reduced protein accretion contributed to lower gastrocnemius mass in ER-fed rats. Lower turnover rates of most muscle proteins in HP-fed rats without reductions in protein pool size (i.e., tissue mass) suggests prolonged HP intake, independent of energy, may prolong muscle protein lifespan of in obese Zucker rats. Funding Sources Supported by USAMRDC; authors’ views not official U.S. Army or DoD policy.

Effects of Two Types of Calorie Restriction on Methylation Levels of Adiponectin Receptor 1 (AdipoR1) and Leptin Receptor Overlapping Transcript (Leprot) in a MMTV-TGF-α Breast Cancer Mouse Model.

The role of adiponectin and leptin signalling pathways has been suggested to play important roles in the protective effects of energy restriction (ER) on mammary tumour (MT) development. To study the effects of ER on the methylation levels in adiponectin receptor 1 (AdipoR1) and leptin receptor overlapping transcript (Leprot) genes using the pyrosequencing method in mammary fat pad tissue, mouse mammary tumour virus-transforming growth factor-α (MMTV-TGF-α) female mice were randomly assigned to ad libitum (AL), chronic ER (CER, 15 % ER) or intermittent ER (3 weeks AL and 1 week 60 % ER in cyclic periods) groups at 10 weeks of age until 82 weeks of age. The methylation levels of AdipoR1 in the CER group were higher than those in the AL group at week 49/50 (P < 0·05), while the levels of methylation for AdipoR1 and Leprot genes were similar among the other groups. Also, the methylation levels at CpG2 and CpG3 regions of the promoter region of the AdipoR1 gene in the CER group were three times higher (P < 0·05), while CpG1 island of Leprot methylation was significantly lower compared with the other groups (P < 0·05). Adiponectin and leptin gene expression levels were consistent with the methylation levels. We also observed a change with ageing in methylation levels of these genes. These results indicate that different types of ER modify methylation levels of AdipoR1 and Leprot in different ways and CER had a more significant effect on methylation levels of both genes. Epigenetic regulation of these genes may play important roles in the preventive effects of ER against MT development and ageing processes.

Effects of two types of energy restriction on methylation levels of adiponectin receptor 1 and leptin receptor overlapping transcript in a mouse mammary tumour virus-transforming growth factor-α breast cancer mouse model.

The role of adiponectin and leptin signalling pathways has been suggested to play important roles in the protective effects of energy restriction (ER) on mammary tumour (MT) development. To study the effects of ER on the methylation levels in adiponectin receptor 1 (AdipoR1) and leptin receptor overlapping transcript (Leprot) genes using the pyrosequencing method in mammary fat pad tissue, mouse mammary tumour virus-transforming growth factor-α (MMTV-TGF-α) female mice were randomly assigned to ad libitum (AL), chronic ER (CER, 15 % ER) or intermittent ER (3weeks AL and 1 week 60 % ER in cyclic periods) groups at 10weeks of age until 82weeks of age. The methylation levels of AdipoR1 in the CER group were higher than those in the AL group at week 49/50 (P < 0·05), while the levels of methylation for AdipoR1 and Leprot genes were similar among the other groups. Also, the methylation levels at CpG2 and CpG3 regions of the promoter region of the AdipoR1 gene in the CER group were three times higher (P < 0·05), while CpG1 island of Leprot methylation was significantly lower compared with the other groups (P < 0·05). Adiponectin and leptin gene expression levels were consistent with the methylation levels. We also observed a change with ageing in methylation levels of these genes. These results indicate that different types of ER modify methylation levels of AdipoR1 and Leprot in different ways and CER had a more significant effect on methylation levels of both genes. Epigenetic regulation of these genes may play important roles in the preventive effects of ER against MT development and ageing processes.

Effect of Energy Restriction on Eating Behavior Traits and Psychobehavioral Factors in the Low Satiety Phenotype.

Studies have shown that individuals with low satiety efficiency may be more susceptible to weight gain, but little is known about the effect of weight loss intervention outcomes in these individuals. This study aimed to evaluate the impact of an energy-restricted weight loss intervention on eating behavior traits and psychobehavioral factors in individuals differing in their satiety responsiveness. A pooled cohort of individuals who were overweight or obese (n = 100; aged 39 ± 9 years) participating in a 12- to 15-week weight loss program targeting an energy deficit of 500–700 kcal/day were included in this study. Satiety responsiveness was determined by a median split of the mean satiety quotient based on appetite sensations measured in response to a test meal at baseline (low satiety responsiveness (LSR) vs. high satiety responsiveness (HSR)). Anthropometric variables, eating behavior traits, psychobehavioral factors, and ad libitum energy intake were assessed before and after the intervention. Although similar weight loss was observed between the LSR and HSR groups (−3.5 ± 3.2 vs. −3.8 ± 2.8 kg, p = 0.64) in response to an energy-restricted weight loss intervention, changes in eating behavior traits were different between groups. Individuals with LSR had a higher increase in cognitive restraint (+5.5 ± 4.1 vs. +3.5 ± 3.5, p = 0.02) and some of its subscales and a lower decrease in situational susceptibility to disinhibition (−0.6 ± 1.1 vs. −1.2 ± 1.3, p = 0.02) in response to the intervention compared to the HSR group. In conclusion, energy-restricted weight loss intervention seems to trigger undesirable changes in some eating behavior traits in individuals more vulnerable to overeating, which could increase their susceptibility to weight regain.

Energy restriction in renal protection.

Energy restriction (ER) has been widely studied as a novel intervention, and its ability to prolong life has been fully demonstrated. For example, ER can significantly extend the lifespans of model flies, worms, rodents and other mammals. The role of ER in renal protection has also been elucidated. In preclinical studies, adjusting total energy intake or consumption of specific nutrients has prophylactic or therapeutic effects on ageing-related kidney disease and acute and chronic kidney injury. Amino acid restriction has gradually attracted attention. ER mimetics have also been studied in depth. The protective mechanisms of ER and ER mimetics for renal injury include increasing AMP-activated protein kinase and sirtuin type 1 (Sirt1) levels and autophagy and reducing mammalian target of rapamycin, inflammation and oxidative stress. However, the renal protective effect of ER has mostly been investigated in rodent models, and the role of ER in patients cannot be determined due to the lack of large randomised controlled trials. To protect the kidney, the mechanism of ER must be thoroughly researched, and more accurate diet or drug interventions need to be identified.

Effects of energy restriction during gilt development on milk nutrient profile, milk oligosaccharides, and progeny biomarkers.

An ongoing study at the University of Nebraska-Lincoln (which included 14 batches of gilts; n = 90 gilts/batch) demonstrated that energy restriction during the developmental period of a gilt increases longevity and may also have beneficial effects on progeny health and growth, particularly, parity 1 progeny. Therefore, we hypothesized that energy restriction during gilt development may affect milk nutrient profile, milk oligosaccharides (OS), and postnatal progeny biomarkers. During the development period, batch 14 gilts (n = 128, 8 gilts/pen) were fed 3 dietary treatments including the following: 1) Control diet formulated to NRC (2012) specifications (CTL); 2) Restricted (20% energy restriction via addition of 40% soy hulls; RESTR); and 3) CTL diet plus addition of crystalline amino acids equivalent to the SID Lys:ME of the RESTR diet (CTL+). All diets were fed ad libitum and applied in a 3-phase feeding regimen during gilt development (days 123 to 230 of age). Average daily feed intake was used to estimate daily metabolizable energy intake (Mcal/d) during each phase (Phase 1: 10.13, 6.97, 9.95; Phase 2: 11.25, 8.05, 10.94; and Phase 3: 9.47, 7.95,11.07) for CTL, RESTR, and CTL+, respectively. After 230 d of age, gilts were bred and fed a common diet. Milk samples were collected from batch 14 gilts (n = 7 per treatment) on days 0 and 14 postfarrowing for compositional analysis of N, CP, dry matter (DM), GE, insulin, and OS. Piglet blood samples (n = 6 piglets/gilt) were obtained on days 1 and 15 postfarrowing for quantification of glucagon-like peptide-2 (GLP-2) and insulin. No effects of developmental diet were observed for milk N, CP, DM, or GE; however, N, CP, DM, and insulin were increased (P < 0.05) on day 1 compared with day 14. A total of 61 different milk OS were identified. Milk OS profile was significantly different for neutral and acidic OS (P < 0.05) on day 0, but there were no significant differences on day 14. For piglet GLP-2, a treatment by day interaction was observed (P < 0.009); specifically, on day 1 GLP concentrations were greater (P < 0.001) in CTL+ compared with RESTR (6.73 vs. 1.21 ng/mL). For serum insulin, a treatment by day interaction was observed (P < 0.01); specifically, insulin in RESTR progeny was greater (P < 0.03) than CTL on day 1. In conclusion, nutritional management of the developing gilt may affect milk nutrient composition, milk OS profile, and piglet serum biomarkers.

Effects of Energy and Carbohydrate Intake on Serum High-Density Lipoprotein-Cholesterol Levels

High-density lipoprotein (HDL) is a lipoprotein which has anti-atherogenic property by reverse cholesterol transport from the peripheral tissues to liver. Low HDL-cholesterol (HDL-C) level is associated with the development of coronary artery diseases. We previously studied effects of energy and carbohydrate intake on serum HDL-C to make “Dietary Reference Intakes for Japanese 2015”, and reported the results by reviewing papers by 2012. Here we review meta-analyses about the effects of energy and carbohydrate intake on serum HDL-C levels which were published from 2012 to 2018, to make “Dietary Reference Intake for Japanese 2020”, by using PubMed, Embase and Google Scholar. Effects of energy restriction on HDL-C may depend on backgrounds of subjects studied, the ratio of carbohydrate, protein and fat. Low carbohydrate diet may increase HDL-C, which may be due to reduction of body weight and/or amelioration of insulin resistance. Regarding intake of free sugar, further studies including effects of free sugar intake on other risk factors in addition to HDL-C should be performed. Fructose intake may exert no effect on HDL-C; however, the fructose intake equal to or less than 100 g/day may be recommended considering unfavorable effects on triglyceride (TG) and low-density lipoprotein-cholesterol (LDL-C). J Endocrinol Metab. 2018;8(2-3):27-31 doi: https://doi.org/10.14740/jem504w