Short-term Energy Restriction Research Articles

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

FRI391 A Metabolomics Analysis Of Moderate Energy Restriction In Healthy Lean Women

Abstract Disclosure: L. Levine: None. K. Overdahl: None. S. Molsberry: None. S. Shekhar: None. A. Jarmusch: None. J.E. Hall: None. Introduction: Metabolomics can elucidate metabolic responses to dietary interventions and has been used in energy restriction studies, primarily in overweight/obese men and women. Although the menstrual cycle affects the metabolome, most dietary intervention studies have not controlled for menstrual cycle phase, nor have they examined the effect of moderate, short-term energy restriction on the metabolic profile of healthy, normal-weight women. Objective: To characterize metabolomic changes in response to a 55% reduction in dietary intake during the early follicular phase of the menstrual cycle. Methods: Study participants included 19 healthy women aged 18-28 years who were of normal BMI and fitness, not restricting nutritional intake and with biochemically confirmed regular ovulatory menstrual cycles. Participants underwent 5-day dietary interventions in the early follicular phase of two menstrual cycles. The first diet consisted of neutral energy availability (NEA; 45 kcal/kg*lean body mass/day) and the second of deficient energy availability (DEA; 20 kcal/kg*lean body mass/day) without changes in macronutrient composition. On the 5th day of each diet, serum was collected at ∼8am following an overnight fast, and immediately before and every 10 minutes for 60 minutes after the consumption of a standardized isocaloric snack at ∼4pm. Untargeted metabolomic profiling was performed using ultra-high performance liquid chromatography/mass spectroscopy. Univariate statistics were performed on all metabolites, using t-tests with Benjamini-Hochberg false discovery rate adjusted p-values to account for multiple testing (p-value ≤ 0.05). Log2-fold change was calculated for all chemical features. Results: At baseline, participants had a weight of 61.9±2.75 kg (mean±SEM), BMI of 23.96±0.69 kg/m2 (mean±SEM), and percent body fat of 28.01±1.61% (mean±SEM). DEA resulted in a 1.25±0.13 kg (mean±SEM) decrease in body weight (p<0.01). While few statistically significant differences were present between fasted NEA and DEA samples, numerous chemical features were significantly upregulated in DEA post-snack samples. Specifically, 11 carnitines, 7 phosphocholines, and 8 fatty acids or fatty acid intermediates exhibited a log2fold change of 0.5 or higher (>40% increase; p ≤ 0.05) in post-snack DEA samples compared to NEA samples. Conclusion: These results strongly suggest that following isocaloric intake, moderate energy restriction in normal-weight, healthy women is associated not only with the use of fat as an energy source, but also with cellular membrane breakdown. Presentation: Friday, June 16, 2023

FRI408 Metabolic Hormone- And Energy-related-factors Are Associated With The Pulsatile LH Secretion Response To Short-term Energy Restriction In Healthy Women

Abstract Disclosure: S. Shekhar: None. J. Tessa Tonleu: None. E.D. Brown: None. C. Okigbo: None. L. Helen: None. A.E. Kim: None. B. Purse: None. D. Zaccaro: None. S.J. Soldin: None. K. Hirsch: None. A. Smith-Ryan: None. J.E. Hall: None. Introduction: Functional hypothalamic amenorrhea is characterized by reproductive dysfunction in a deficient energy state mediated through suppressed secretion of pulsatile GnRH. We investigated the relationship between metabolic, appetite, energy, body composition and attitude variables with LH pulse frequency responses. Methods: Two 5-day dietary interventions were administered to nineteen regularly cycling, healthy women (mean age (SD): 23.36 (2.08) y) with unchanged exercise in the early follicular phases of two menstrual cycles. The neutral energy availability diet (NEA, 45 kCal/kg*LBM/d, ±0%) was followed by a deficient energy availability (DEA, -55%) intervention. On enrollment, we administered the following questionnaires: almost perfect, perceived stress, dysfunctional attitude, eating attitudes, exercise (IPAQ), appetite, and palatability. Resting energy expenditure (REE), maximum oxygen uptake (VO2 max) and body composition were assessed at baseline. After each intervention, blood was sampled every 10 min for LH and metabolic hormones (thyroid hormones, GH, cortisol, glucose, insulin, leptin, and orexin) was measured at varying intervals (0800 — 1600hrs). Outcomes included 1) DEA LH pulse frequency expressed as an absolute number (LHPF), 2) change from NEA (αLHPF) and 3) % change from NEA (%αLHPF). Principal components (PC) analysis tested the association between predictor variables separated into relevant domains. As expected from the degree of energy restriction, LHPF decreased in response to DEA in ∼53% of women (‘responders’, n=10) for whom PC analysis was separately performed. Results: For the entire group, the PC for energy expenditure domain highlighted VO2 max and REE and was significantly associated with αLHPF (p=0.04) and %αLHPF (p=0.05). There was no relationship between metabolic or thyroid hormone, or body composition domains with DEA LHPF, αLHPF and %αLHPF. In responders, the fasting metabolic domain primarily consisted of insulin and leptin and was associated with αLHPF (p=0.008) and %αLHPF (p=0.08). The thyroid domain, which was a primary composite of T3, reverse T3 and T4 had a trend of association with DEA LHPF (p=0.06) and %αLHPF (p=0.05). The metabolic domain primarily consisted of samples from the across-the-day growth hormone and cortisol and was associated with αLHPF (p=0.05) and %αLHPF (p=0.049). There was no association between attitude, anthropometry, or energy domains and outcome variables in this subgroup. Conclusion: Our data suggest that in normal women higher resting energy expenditure and a greater degree of fitness predict a greater inhibitory effect of energy restriction on the reproductive axis. In those who demonstrate this inhibition, the degree of response to ER can be predicted by the fasting metabolic (insulin and leptin) and thyroid domains. Presentation: Friday, June 16, 2023

Dose-Response of Myofibrillar Protein Synthesis To Ingested Whey Protein During Energy Restriction in Overweight Postmenopausal Women: A Randomized, Controlled Trial

BackgroundDiet-induced weight loss is associated with a decline in lean body mass, as mediated by an impaired response of muscle protein synthesis (MPS). The dose-response of MPS to ingested protein, with or without resistance exercise, is well characterized during energy balance but limited data exist under conditions of energy restriction in clinical populations. ObjectiveTo determine the dose-response of MPS to ingested whey protein following short-term diet-induced energy restriction in overweight, postmenopausal, women at rest and postexercise. DesignForty middle-aged (58.6±0.4 y), overweight (BMI: 28.6±0.4), postmenopausal women were randomly assigned to 1 of 4 groups: Three groups underwent 5 d of energy restriction (∼800 kcal/d). On day 6, participants performed a unilateral leg resistance exercise bout before ingesting either a bolus of 15g (ERW15, n = 10), 35g (ERW35, n = 10) or 60g (ERW60, n = 10) of whey protein. The fourth group (n = 10) ingested a 35g whey protein bolus after 5 d of an energy balanced diet (EBW35, n = 10). Myofibrillar fractional synthetic rate (FSR) was calculated under basal, fed (FED) and postexercise (FED-EX) conditions by combining an L-[ring-13C6] phenylalanine tracer infusion with the collection of bilateral muscle biopsies. ResultsMyofibrillar FSR was greater in ERW35 (0.043±0.003%/h, P = 0.013) and ERW60 (0.042±0.003%/h, P = 0.026) than ERW15 (0.032 ± 0.003%/h), with no differences between ERW35 and ERW60 (P = 1.000). Myofibrillar FSR was greater in FED (0.044 ± 0.003%/h, P < 0.001) and FED-EX (0.048 ± 0.003%/h, P < 0.001) than BASAL (0.027 ± 0.003%/h), but no differences were detected between FED and FED-EX (P = 0.732) conditions. No differences in myofibrillar FSR were observed between EBW35 (0.042 ± 0.003%/h) and ERW35 (0.043 ± 0.003%/h, P = 0.744). ConclusionA 35 g dose of whey protein, ingested with or without resistance exercise, is sufficient to stimulate a maximal acute response of MPS following short-term energy restriction in overweight, postmenopausal women, and thus may provide a per serving protein recommendation to mitigate muscle loss during a weight loss program. Trial registryclinicaltrials.gov (ID: NCT03326284).

Short-Term Moderate Energy Restriction Does Not Affect Indicators of Oxidative Stress and Genotoxicity in Humans

Restriction of energy intake (ER), without malnutrition of essential nutrients, has repeatedly been demonstrated to increase longevity in rodents. In the antioxidant theory of aging the lack of balance between the generation of free radicals and free radical scavenging was thought to be a main causal agent in the aging process. From this point of view the antiaging effect induced by ER might be due to the lower rate of free-radical production and related damage induced by a lower metabolic rate. The antiaging effects of ER might also occur in humans. This study explored the effects of a 10-week moderately energy-restricted diet (80% of habitual) in 24 non-obese middle-aged men (16 ER subjects, 8 controls) on resting metabolic rate (RMR) and indicators of the primary antioxidant defense system, oxidative stress and genotoxicity. RMR decreased significantly in both groups, even when adjustments were made for the change in body composition. The increase in blood vitamin C concentrations correlated with the increase in urinary 8-hydroxy-deoxyguanosine (80HdG) excretion. The change in urinary 80HdG excretion also correlated with the change in RMR per kg fat-free mass. No differences between groups were found for changes in indicators of genotoxicity, erythrocyte catalase, glutathione peroxidase and superoxide dismutase activity and in plasma vitamin E, A or β-carotene concentrations. We conclude that 10 weeks of moderate ER did not affect indicators of antioxidative capacity, oxidative stress and genotoxicity of humans. Since subjects were not in energy balance at the end of the study, no conclusions can be made with respect to long-term effects.

Abstract #1004271: The Effect of Short-term Energy Restriction on Appetite

Abstract #1004271: The Effect of Short-term Energy Restriction on Appetite

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.

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.

Divergent Changes in Plasma AGEs and sRAGE Isoforms Following an Overnight Fast in T1DM.

Advanced glycation end products (AGEs) promote the development of diabetic complications through activation of their receptor (RAGE). Isoforms of soluble RAGE (sRAGE) sequester AGEs and protect against RAGE-mediated diabetic complications. We investigated the effect of an overnight fast on circulating metabolic substrates, hormones, AGEs, and sRAGE isoforms in 26 individuals with type 1 diabetes (T1DM). Blood was collected from 26 young (18–30 years) T1DM patients on insulin pumps before and after an overnight fast. Circulating AGEs were measured via LC-MS/MS and sRAGE isoforms were analyzed via ELISA. Glucose, insulin, glucagon, and eGFRcystatin-c decreased while cortisol increased following the overnight fast (p < 0.05). AGEs (CML, CEL, 3DG-H, MG-H1, and G-H1) decreased (21–58%, p < 0.0001) while total sRAGE, cleaved RAGE (cRAGE), and endogenous secretory RAGE (esRAGE) increased (22–24%, p < 0.0001) following the overnight fast. The changes in sRAGE isoforms were inversely related to MG-H1 (rho = −0.493 to −0.589, p < 0.05) and the change in esRAGE was inversely related to the change in G-H1 (rho = −0.474, p < 0.05). Multiple regression analyses revealed a 1 pg/mL increase in total sRAGE, cRAGE, or esRAGE independently predicted a 0.42–0.52 nmol/L decrease in MG-H1. Short-term energy restriction via an overnight fast resulted in increased sRAGE isoforms and may be protective against AGE accumulation.

Impact of energy restriction during late gestation on the muscle and blood transcriptome of beef calves after preconditioning

BackgroundMaternal nutrition has been highlighted as one of the main factors affecting intra-uterine environment. The increase in nutritional requirements by beef cows during late gestation can cause nutritional deficiency in the fetus and impact the fetal regulation of genes associated with myogenesis and immune response.MethodsForty days before the expected calving date, cows were assigned to one of two diets: 100% (control) or 70% (restricted group) of the daily energy requirement. Muscle samples were collected from 12 heifers and 12 steers, and blood samples were collected from 12 steers. The objective of this work was to identify and to assess the biological relevance of differentially expressed genes (DEG) in the skeletal muscle and blood of beef calves born from cows that experienced [or not] a 30% energy restriction during the last 40 days of gestation.ResultsA total of 160, 164, and 346 DEG (q-value< 0.05) were identified in the skeletal muscle for the effects of diet, sex, and diet-by-sex interaction, respectively. For blood, 452, 1392, and 155 DEG were identified for the effects of diet, time, and diet-by-time interaction, respectively. For skeletal muscle, results based on diet identified genes involved in muscle metabolism. In muscle, from the 10 most DEG down-regulated in the energy-restricted group (REST), we identified 5 genes associated with muscle metabolism and development: SLCO3A1, ATP6V0D1, SLC2A1, GPC4, and RASD2. In blood, among the 10 most DEG, we found genes related to response to stress up-regulated in the REST after weaning, such as SOD3 and INO80D, and to immune response down-regulated in the REST after vaccination, such as OASL, KLRF1, and LOC104968634.ConclusionIn conclusion, maternal energy restriction during late gestation may limit the expression of genes in the muscle and increase expression in the blood of calves. In addition, enrichment analysis showed that a short-term maternal energy restriction during pregnancy affects the expression of genes related to energy metabolism and muscle contraction, and immunity and stress response in the blood. Therefore, alterations in the intra-uterine environment can modify prenatal development with lasting consequences to adult life.

Pilot Study Examining the Influence of Potassium Bicarbonate Supplementation on Nitrogen Balance and Whole-Body Ammonia and Urea Turnover Following Short-Term Energy Restriction in Older Men.

With aging there is a chronic low-grade metabolic-acidosis that may exacerbate negative protein balance during weight loss. The objective of this randomized pilot study was to assess the impact of 90 mmol∙day−1 potassium bicarbonate (KHCO3) versus a placebo (PLA) on 24-h urinary net acid excretion (NAE), nitrogen balance (NBAL), and whole-body ammonia and urea turnover following short-term diet-induced weight loss. Sixteen (KHCO3; n = 8, PLA; n = 8) older (64 ± 4 years) overweight (BMI: 28.5 ± 2.1 kg∙day−1) men completed a 35-day controlled feeding study, with a 7-day weight-maintenance phase followed by a 28-day 30% energy-restriction phase. KHCO3 or PLA supplementation began during energy restriction. NAE, NBAL, and whole-body ammonia and urea turnover (15N-glycine) were measured at the end of the weight-maintenance and energy-restriction phases. Following energy restriction, NAE was −9.8 ± 27.8 mmol∙day−1 in KHCO3 and 43.9 ± 27.8 mmol∙day−1 in PLA (p < 0.05). No significant group or time differences were observed in NBAL or ammonia and urea turnover. Ammonia synthesis and breakdown tended (p = 0.09) to be higher in KHCO3 vs. PLA following energy restriction, and NAE was inversely associated (r = −0.522; p < 0.05) with urea synthesis in all subjects. This pilot study suggests some benefit may exist with KHCO3 supplementation following energy restriction as lower NAE indicated higher urea synthesis.

Effect of Lorcaserin Alone and in Combination with Phentermine on Food Cravings After 12-Week Treatment: A Randomized Substudy.

ObjectiveThis study evaluated the effect of lorcaserin 10mg twice daily (LOR BID) or with phentermine, 15mg/day (LOR BID+PHEN QD) and 15mg twice daily (LOR BID+PHEN BID) in conjunction with energy restriction, on food cravings.Methods235 patients without diabetes, but with obesity or overweight and ≥1 comorbidity received (LOR BID), (LOR BID+PHEN QD), or (LOR BID+PHEN BID) for 12 weeks, in a randomized double-blind study. The Food Craving Inventory (FCI) and the Control of Eating Questionnaire (COEQ) were administered over 12 weeks.ResultsThe FCI total score and the subscale scores reduced from baseline in all groups. The least squares means (95% confidence intervals) for the total scores were −0.65 (−0.75, −0.55), −0.75 (−0.84, −0.65), and −0.84 (−0.95, −0.74) in the LOR BID, LOR BID+PHEN QD, and LOR BID+PHEN BID groups, respectively. Cravings assessed by COEQ reduced from baseline in all groups. In general, the combination treatments were more effective than lorcaserin alone. At week 12, except for fruit juice and dairy products, general and specific cravings reduced in LOR BID+PHEN BID compared to LOR BID (p<0.05).ConclusionsLorcaserin in combination with phentermine improves control of food cravings during short-term energy restriction.

Upregulation of circulating myomiR following short-term energy restriction is inversely associated with whole body protein synthesis.

The objective of the present investigation was to determine whether energy restriction (ER) influences expression of skeletal muscle-specific microRNA (miRNA) in circulation (c-myomiR) and whether changes in c-myomiR are associated with rates of whole body protein synthesis. Sixteen older (64 ± 2 yr) overweight (28.5 ± 1.2 kg/m2) men enrolled in this 35-day controlled feeding trial. A 7-day weight maintenance (WM) period was followed by 28 days of 30% ER. Whole body protein turnover was determined from [15N]glycine enrichments in 24-h urine collections, and c-myomiR (miR-1-3p, miR-133a-3p, miR-133b, and miR-206) expression was assessed from serum samples by RT-quantitative PCR upon completion of the WM and ER periods. Participants lost 4.4 ± 0.3 kg body mass during ER (P < 0.05). After 28 days of ER, miR-133a and miR-133b expression was upregulated (P < 0.05) compared with WM. When all four c-myomiR were grouped as c-myomiR score (sum of the median fold change of all myomiR), overall expression of c-myomiR was higher (P < 0.05) at ER than WM. Backward linear regression analysis of whole body protein synthesis and breakdown and carbohydrate, fat, and protein oxidation determined protein synthesis to be the strongest predictor of c-myomiR score. An inverse association (P < 0.05) was observed with ER c-myomiR score and whole body protein synthesis (r = -0.729, r2 = -0.530). Findings from the present investigation provide evidence that upregulation of c-myomiR expression profiles in response to short-term ER is associated with lower rates of whole body protein synthesis.

Short-term energy restriction during late gestation of beef cows decreases postweaning calf humoral immune response to vaccination.

Our objectives were to evaluate the pre- and postweaning growth and measurements of innate and humoral immune response of beef calves born to cows fed 70 or 100% of NEm requirements during the last 40 d of gestation. On d 0 (approximately 40 d before calving), 30 multiparous Angus cows pregnant to embryo transfer (BW = 631 ± 15 kg; age = 5.2 ± 0.98 yr; BCS = 6.3 ± 0.12) were randomly allocated into 1 of 10 drylot pens (3 cows/pen). Treatments were randomly assigned to pens (5 pens/treatment) and consisted of cows limit-fed (d 0 to calving) isonitrogenous, total-mixed diets formulated to provide 100 (CTRL) or 70% (REST) of daily NEm requirements of a 630-kg beef cow at 8 mo of gestation. Immediately after calving, all cow-calf pairs were combined into a single management group and rotationally grazed on tall fescue pastures (6 pastures; 22 ha/pasture) until weaning (d 266). All calves were assigned to a 40-d preconditioning period in a drylot from d 266 to 306 and vaccinated against infectious bovine rhinotracheitis, bovine viral diarrhea virus (BVDV), , and spp. on d 273 and 287. Blood samples from jugular vein were collected from cows on d 0, 17, and 35 and from calves within 12 h of birth and on d 266, 273, 274, 276, 279, and 287. By design, REST cows consumed less ( ≤ 0.002) total DMI, TDN, and NEm but had similar CP intake ( = 0.67), which tended ( = 0.06) to increase BW loss from d 0 to calving, than CTRL cows (-1.09 vs. -0.70 ± 0.14 kg/d, respectively). However, gestational NEm intake did not affect ( ≥ 0.30) plasma concentrations of cortisol, insulin, and glucose during gestation and BCS at calving as well as postcalving pregnancy rate, BW, and BCS change of cows. Calf serum IgG concentrations and plasma concentrations of haptoglobin and cortisol at birth as well as calf pre- and postweaning BW and ADG did not differ ( ≥ 0.15) between calves born to REST and CTRL cows. However, calf postweaning overall plasma concentrations of cortisol; plasma haptoglobin concentrations on d 274, 276, and 279; and serum BVDV-1a titers on d 306 were less for REST calves than for CTRL calves ( ≤ 0.05). Hence, a NEm restriction to 70% of daily requirements during the last 40 d of gestation had minimal effects on cow precalving growth and did not affect postcalving cow growth and reproductive performance. However, it decreased postweaning vaccination-induced humoral immunity, inflammatory, and physiological stress responses of calves.

Resting energy expenditure adaptation after short-term caloric restriction in morbidly obese women

Objective:The objective of this study was to describe changes in the resting energy expenditure, substrate oxidation rate, and body composition in morbidly obese women subjected to short-term caloric restriction. Methods:This was a prospective study that included ten obese women with body mass index greater than 40 kg/m2 and aged between 20-50 years. The participants were hospitalized for eight days and received a controlled conventional low-calorie diet, 1200 kcal/day, for seven days. Body weight, body mass index, abdominal circumference, body composition, resting energy expenditure, and substrate oxidation rate were evaluated at the beginning and at the end of the study. Results:A significant reduction in body weight (p=0.005), body mass index (p=0.005), abdominal circumference (p=0.005), fat mass (p=0.005) and fat-free mass (p=0.008) was observed at the end of the study. There was an average reduction in resting energy expenditure of approximately 124 kcal/day (5%). Substrate oxidation rate did not show statistically significant changes. There was a positive correlation only between body weight reduction and fat-free mass reduction (r=0.753; p=0.012). Conclusion:There was an adaptive response of the resting energy expenditure with short-term energy restriction in morbidly obese women with a 5% reduction in resting energy expenditure and a positive correlation between weight loss and the fat-free mass, which indicates the influence of fat-free mass on the decrease in resting energy expenditure. Therefore, short-term caloric restriction in morbidly obese women led to a decrease in resting energy expenditure and fat-free mass, which suggests a rapid adaptation of energy expenditure.

Erratum for Hector et al. Whey protein supplementation preserves postprandial myofibrillar protein synthesis during short-term energy restriction in overweight and obese adults. J Nutr 2015;145:246–52.

Erratum for Hector et al. Whey protein supplementation preserves postprandial myofibrillar protein synthesis during short-term energy restriction in overweight and obese adults. J Nutr 2015;145:246–52.

Whey Protein Supplementation Preserves Postprandial Myofibrillar Protein Synthesis during Short-Term Energy Restriction in Overweight and Obese Adults1–3

Background: Higher dietary energy as protein during weight loss results in a greater loss of fat mass and retention of muscle mass; however, the impact of protein quality on the rates of myofibrillar protein synthesis (MPS) and lipolysis, processes that are important in the maintenance of muscle and loss of fat, respectively, are unknown.Objective: We aimed to determine how the consumption of different sources of proteins (soy or whey) during a controlled short-term (14-d) hypoenergetic diet affected MPS and lipolysis.Methods: Men (n = 19) and women (n = 21) (age 35–65 y; body mass index 28–50 kg/m2) completed a 14-d controlled hypoenergetic diet (−750 kcal/d). Participants were randomly assigned, double blind, to receive twice-daily supplements of isolated whey (27 g/supplement) or soy (26g/supplement), providing a total protein intake of 1.3 ± 0.1 g/(kg · d), or isoenergetic carbohydrate (25 g maltodextrin/supplement) resulting in a total protein intake of 0.7 ± 0.1 g/(kg · d). Before and after the dietary intervention, primed continuous infusions of L-[ring-13C6] phenylalanine and [2H5]-glycerol were used to measure postabsorptive and postprandial rates of MPS and lipolysis.Results: Preintervention, MPS was stimulated more (P < 0.05) with ingestion of whey than with soy or carbohydrate. Postintervention, postabsorptive MPS decreased similarly in all groups (all P < 0.05). Postprandial MPS was reduced by 9 ± 1% in the whey group, which was less (P < 0.05) than the reduction in soy and carbohydrate groups (28 ± 5% and 31 ± 5%, respectively; both P < 0.05) after the intervention. Lipolysis was suppressed during the postprandial period (P < 0.05), but more so with ingestion of carbohydrate (P < 0.05) than soy or whey.Conclusion: We conclude that whey protein supplementation attenuated the decline in postprandial rates of MPS after weight loss, which may be of importance in the preservation of lean mass during longer-term weight loss interventions. This trial was registered at clinicaltrials.gov as NCT01530646.

Effects of energy restriction on activity of the hypothalamo-pituitary-adrenal axis in obese humans and rodents: implications for diet-induced changes in body composition.

Obesity treatments aim to maximize fat loss, particularly abdominal or visceral fat, without compromising lean or bone mass. However, the literature contains numerous examples of obesity treatments that - in addition to fat loss - result in loss of lean mass and/or bone mass. Because of the known effects of energy restriction to increase activity of the hypothalamo-pitutiary adrenal (HPA) axis in lean humans and animals, and because increases in circulating glucocorticoid levels could potentially contribute to adverse body compositional changes with obesity treatments, we conducted a systematic PubMed search to determine whether HPA axis activation also occurs in response to energy restriction in obese humans and animals. In most studies in obese humans, short-term severe energy restriction increased circulating cortisol levels, and this response was also seen in two longer-term human studies involving severe or moderate energy restriction. These findings parallel studies on short- or long-term energy restriction in obese rodents, with most studies showing increases in circulating corticosterone concentrations, and no change or actual increases in hypothalamic expression of corticotropin-releasing hormone, urocortin 3 or their receptors. However, a significant proportion of studies involving longer-term severe or moderate energy restriction in obese humans showed no change or decreases in HPA axis function. There was variability among human studies in the duration of energy restriction and timing of the HPA axis investigations (i.e., during energy restriction, or after a period of post-restriction weight maintenance). In order to unambiguously determine changes in HPA axis function with energy restriction in obese humans, it will be important to assess HPA axis function at multiple time points during energy restriction, given that obese individuals may spend many weeks or months in severe or moderate energy restriction in order to reduce excess weight, and given that increases in glucocorticoid function can have significant effects on body composition within weeks to months.

An Experimental Model for Resistance Exercise in Rodents

This study aimed to develop an equipment and system of resistance exercise (RE), based on squat-type exercise for rodents, with control of training variables. We developed an operant conditioning system composed of sound, light and feeding devices that allowed optimized RE performance by the animal. With this system, it is not necessary to impose fasting or electric shock for the animal to perform the task proposed (muscle contraction). Furthermore, it is possible to perform muscle function tests in vivo within the context of the exercise proposed and control variables such as intensity, volume (sets and repetitions), and exercise session length, rest interval between sets and repetitions, and concentric strength. Based on the experiments conducted, we demonstrated that the model proposed is able to perform more specific control of other RE variables, especially rest interval between sets and repetitions, and encourages the animal to exercise through short-term energy restriction and “disturbing” stimulus that do not promote alterations in body weight. Therefore, despite experimental limitations, we believe that this RE apparatus is closer to the physiological context observed in humans.

Dietary fat and not calcium supplementation or dairy product consumption is associated with changes in anthropometrics during a randomized, placebo-controlled energy-restriction trial

Insufficient calcium intake has been proposed to cause unbalanced energy partitioning leading to obesity. However, weight loss interventions including dietary calcium or dairy product consumption have not reported changes in lipid metabolism measured by the plasma lipidome.MethodsThe objective of this study was to determine the relationships between dairy product or supplemental calcium intake with changes in the plasma lipidome and body composition during energy restriction. A secondary objective of this study was to explore the relationships among calculated macronutrient composition of the energy restricted diet to changes in the plasma lipidome, and body composition during energy restriction. Overweight adults (n = 61) were randomized into one of three intervention groups including a deficit of 500kcal/d: 1) placebo; 2) 900 mg/d calcium supplement; and 3) 3-4 servings of dairy products/d plus a placebo supplement. Plasma fatty acid methyl esters of cholesterol ester, diacylglycerol, free fatty acids, lysophosphatidylcholine, phosphatidylcholine, phosphatidylethanolamine and triacylglycerol were quantified by capillary gas chromatography.ResultsAfter adjustments for energy and protein (g/d) intake, there was no significant effect of treatment on changes in weight, waist circumference or body composition. Plasma lipidome did not differ among dietary treatment groups. Stepwise regression identified correlations between reported intake of monounsaturated fat (% of energy) and changes in % lean mass (r = -0.44, P < 0.01) and % body fat (r = 0.48, P < 0.001). Polyunsaturated fat intake was associated with the % change in waist circumference (r = 0.44, P < 0.01). Dietary saturated fat was not associated with any changes in anthropometrics or the plasma lipidome.ConclusionsDairy product consumption or calcium supplementation during energy restriction over the course of 12 weeks did not affect plasma lipids. Independent of calcium and dairy product consumption, short-term energy restriction altered body composition. Reported dietary fat composition of energy restricted diets was associated with the degree of change in body composition in these overweight and obese individuals.