Dietary Energy, Glucocorticoids and the Regulation of Long Bone and Muscle Growth in the Rat

1994 ◽  
Vol 87 (5) ◽  
pp. 599-606 ◽  
Author(s):  
J. O. Tirapegui ◽  
Z. A. H. Yahya ◽  
P. C. Bates ◽  
D. Joe Millward

1. The influence of dietary energy restriction and corticosterone on long bone and muscle growth, and their interrelationships, was studied in rats fed a range of restricted amounts of diets containing increasing concentrations of protein, thus maintaining constant protein intakes. Tibial length and epiphyseal cartilage width were measured radiographically. 2. In experiment 1, tibial length and gastrocnemius muscle growth were examined in ad libitum fed rats and during 4 days of severe energy restriction (25% ad libitum intake), starvation and ad libitum feeding with corticosterone treatment (10 mg/100 g), a mediator of the response to energy restriction. Weight loss occurred in all groups. Tibial growth continued in the 25% and starvation groups albeit at reduced rates with the inhibition of starvation > 25% group (P < 0.05), but was arrested after 2 days of corticosterone treatment. 3. Muscle growth inhibition was proportional to tibial growth inhibition of the 25% group, insofar as the muscle/bone ratio (W/L3.85), was maintained. This inter-relationship between muscle and bone growth previously reported for ad libitum high-protein-fed rats, is likely to reflect the anabolic influence of bone on muscle via passive muscle stretching induced by length growth. For both starvation and corticosterone groups the muscle/bone ratio fell (P < 0.05 compared with the ad libitum group), suggesting that muscle growth inhibition included an additional direct catabolic influence of starvation and corticosterone treatment. 4. In experiment 2, measurements of bone, muscle and liver growth were made in rats fed 75%, 50% and 25% ad libitum intakes and fed ad libitum intakes with corticosterone treatment for 8 days. Although body weight growth was arrested in all groups with weight loss in the 50%, 25% and corticosterone groups (P < 0.05), some tibial length growth continued at all levels of energy restriction, with significant reductions in length in the 50% and 25% groups at 4 days and in all groups at 8 days. Corticosterone treatment immediately arrested length growth. The epiphyseal cartilage widths of all restricted groups were significantly reduced at 4 days, graded with the degree of restriction, with corticosterone treatment most marked. 5. Muscle growth continued at near normal rates in the 75% and 50% groups, slowing only after 4 days, but was arrested in the corticosterone and 25% group with weight loss by 4 days in the corticosterone group and after 4 days in the 25% group. Muscle growth appeared relatively resistant to direct inhibition by energy restriction, following tibial growth in all restricted groups in that the muscle/bone ratios were initially maintained in all energy-restricted groups, falling only with the corticosterone treatment or 8 days of 50% and 25% intakes. In contrast, liver lost weight in all restricted groups during the first 4 days. 6. The results show a graded delayed inhibitory influence of energy deficiency on bone growth, which may be mediated by corticosteroids given the marked inhibitory influence of corticosterone. The relative resistance of muscle growth to energy restriction during liver and body-weight loss, is consistent with a powerful physiological anabolic stimulus of muscle stretching by bone length growth that appears to override any dietary-induced catabolic influence.

1994 ◽  
Vol 87 (5) ◽  
pp. 607-618 ◽  
Author(s):  
Z. A. H. Yahya ◽  
J. O. Tirapegui ◽  
P. C. Bates ◽  
D. Joe Millward

1. We report here the extent to which changes in protein turnover contribute to the previously described inhibition of growth of rat tibial length and skeletal muscle mass in response to protein deficiency [1], energy restriction and corticosterone treatment [2]. Measurements of 35S uptake in vivo also enabled the qualitative pattern of changes in proteoglycan synthesis in bone and muscle to be established. 2. Protein deficiency was examined by ad libitum feeding of 20%, 7%, 3.5% and 0.5% protein diets with measurements at 1, 3 and 7 days (all diets), and 14 and 21 days (0.5% protein). In bone this induced delayed inhibition of tibial growth with parallel inhibition of protein synthesis, as measured by the phenylalanine flooding dose method. This was mediated by reductions in both ribosomal capacity (RNA/protein ratio) and activity (protein synthesis/RNA) in the 0.5% protein group. The pattern of inhibition of proteoglycan sulphation, measured as 35S uptake 60 min after injection of a tracer dose of labelled sulphate, was similar to that of protein synthesis. 3. In muscle there was an intermediate graded inhibition of protein synthesis by protein deficiency, mediated by reductions in both ribosomal capacity and activity in the 0.5% protein group, which preceded growth inhibition in the 7% and 3.5% groups, and which was progressive with time. Transient increases in proteolysis contributed to the growth inhibition is some groups, but the rate fell eventually in the 0.5% group. The pattern of response of proteoglycan sulphation differed from protein synthesis with a delayed inhibition, but with subsequent marked reduction. 4. Energy restriction was induced by diets fed for 4 or 8 days at 75%, 50% and 25% ad libitum intakes with protein intakes held constant, and corticosterone treatment involved a dose of 10 mg day−1 100−1 g (subcutaneous) with ad libitum feeding. In bone this induced a pattern of length growth inhibition which was dissociated from inhibition of protein synthesis in the moderately restricted (75% and 50%) groups. Only in the 25% group and in the 8 day corticosterone group was protein synthesis inhibited, through reductions in ribosomal capacity and activity. 35S uptake was also dissociated from growth inhibition, with reduced 35S uptake observed only after corticosterone treatment or 8 days of the 50% or 25% diets. 5. In muscle the energy restriction and corticosterone treatment induced parallel inhibitions of growth and protein synthesis, mediated by similar graded reductions in the RNA/protein ratios and in the 25% group in the KRNA. Proteolysis was unchanged in all except the 4-day corticosterone group (elevated by 25%) and the day 8 25% group (elevated by 40%) and corticosterone group (elevated by 60%). 35S uptake was inhibited in parallel to muscle growth and protein synthesis. 6. These data show that inhibition of protein synthesis and 35S uptake is an invariable element of muscle growth inhibition, and a usual but not invariable element of bone growth inhibition. Partial correlation analysis of the interactions between dietary protein, bone growth and muscle protein and proteoglycan synthesis shows that bone growth (as indicated by epiphyseal cartilage width) is significantly correlated with muscle protein synthesis and especially 35S uptake, suggesting that the regulation of muscle growth by passive stretch consequent on bone lengthening includes muscle connective tissue growth as an important target.


Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2128
Author(s):  
Marina Martín ◽  
Amaia Rodríguez ◽  
Javier Gómez-Ambrosi ◽  
Beatriz Ramírez ◽  
Sara Becerril ◽  
...  

Energy restriction is a first therapy in the treatment of obesity, but the underlying biological mechanisms have not been completely clarified. We analyzed the effects of restriction of high-fat diet (HFD) on weight loss, circulating gut hormone levels and expression of hypothalamic neuropeptides. Ten-week-old male Wistar rats (n = 40) were randomly distributed into four groups: two fed ad libitum a normal diet (ND) (N group) or a HFD (H group) and two subjected to a 25% caloric restriction of ND (NR group) or HFD (HR group) for 9 weeks. A 25% restriction of HFD over 9 weeks leads to a 36% weight loss with regard to the group fed HFD ad libitum accompanied by normal values in adiposity index and food efficiency ratio (FER). This restriction also carried the normalization of NPY, AgRP and POMC hypothalamic mRNA expression, without changes in CART. Caloric restriction did not succeed in improving glucose homeostasis but reduced HFD-induced hyperinsulinemia. In conclusion, 25% restriction of HFD reduced adiposity and improved metabolism in experimental obesity, without changes in glycemia. Restriction of the HFD triggered the normalization of hypothalamic NPY, AgRP and POMC expression, as well as ghrelin and leptin levels.


1994 ◽  
Vol 87 (2) ◽  
pp. 213-224 ◽  
Author(s):  
Z. A. H. Yayha ◽  
D. Joe Millward

1. We report here studies of the interrelationship of bone and muscle growth in the rat and the regulatory role of dietary protein. Two experiments were undertaken. In experiment 1, growth inhibition was induced by ad libitum feeding of low protein diets containing 7%, 3.5% or 0.5% protein, with a control group fed a 20% protein diet. Measurements were made at 1, 3 and 7 days. In experiment 2, complete growth inhibition was induced by ad libitum feeding of a 0.5% protein diet with measurements at 7, 14 and 21 days followed by refeeding diets of 3%, 6%, 9%, 12% and 20% protein, with measurements after 3, 7, 10 and 14 days of refeeding (experimental days 24, 28, 31 and 35). Controls fed a 20% protein diet were studied at 0, 14, 21, 24, 28, 31 and 35 days. 2. Body weight growth stopped immediately in all reduced protein groups, with subsequent weight maintenance on the 7% protein diet, slight loss on the 3.5% protein diet or marked weight loss on the 0.5% protein diet, although food intake was maintained for 3 days, falling in all groups after this time. Inhibition of muscle growth was delayed in the 7% and 3.5% protein fed groups, with 12–15% increases in muscle weight after 7 days, but prompt growth inhibition occurred with the 0.5% protein diet with subsequent weight loss. In animals fed the control 20% protein diet, muscle weight (W) reflected tibial length (L) as W = L3.85/102.93 (r = 0.98, n = 98). Calculation of the muscle weight/bone length ratio (μg/mm3.85) indicated that a significant muscle deficit was apparent on day 3 and subsequently in the 0.5% protein fed rats, but not until day 7 in the 3.5% and 7% protein fed animals. 3. Total tibial length, epiphysis length and epiphyseal cartilage width were measured radiographically. In all groups there was no significant reduction in bone length growth during the first 3 days. After 3 days there were graded reductions on reduced protein intakes with complete inhibition on the 0.5% protein diet. Epiphyseal cartilage width responded sensitively, with a reduction within 24 h of the 0.5% and the 3.5% protein diets, and within 3 days of the 7% protein diet. The epiphysis length was only minimally affected. 4. In experiment 2, food intake increased immediately on refeeding in all except the 3% protein fed group. Accelerated body weight growth occurred in the 20%, 12% and 9% protein fed groups, slower growth in the 6% protein fed and little growth in the 3% protein fed group. Muscle growth commenced immediately in all groups, continuing at an accelerated rate in the 20%, 12% and 9% protein fed groups, at a slower but substantial rate in the 6% fed group and with little further growth in the 3% fed group. This allowed muscle repletion in relation to tibial length (i.e. μg/mm3.85) by day 7 in 9%, 12% and 20% fed protein groups. 5. Bone growth recovered slowly on refeeding, in a graded manner with the protein intakes. Significant increases in tibial length were only observed after 7 days of refeeding with 7–10 days required to fully restore growth in the 20% protein fed group and 10–14 days for the 12% and 9% protein fed groups. Only 50% of the age control rate was achieved in the 6% protein fed group, with little growth in the 3% protein fed group. Although gradual restoration of the epiphyseal cartilage width occurred in a graded manner with increasing protein intakes, complete restoration did not occur in any group. The small reduction in epiphysis length was partially, although not entirely, reversed by refeeding. 6. These studies demonstrate an anabolic drive of dietary protein on bone growth which responds in a graded manner to protein intake at levels in excess of those necessary for maximal rates of muscle growth. Muscle growth appears to be dependent in part on bone length growth, possibly through the anabolic influence of passive muscle stretch.


2019 ◽  
Vol 150 (3) ◽  
pp. 623-633 ◽  
Author(s):  
Kristine Beaulieu ◽  
Nuno Casanova ◽  
Pauline Oustric ◽  
Jake Turicchi ◽  
Catherine Gibbons ◽  
...  

ABSTRACT Background Continuous energy restriction (CER) is purported to be problematic because of reductions in fat-free mass (FFM), compensatory motivation to overeat, and weakened satiety. Intermittent energy restriction (IER) is an alternative behavioral weight loss (WL) strategy that may mitigate some of these limitations. Objective The objective of the DIVA study was to compare the effects of CER and IER on appetite when the degree of WL (≥5%) is matched. Methods Women with overweight/obesity (BMI 25.0–34.9 kg/m2; age 18–55 y) were recruited for this controlled-feeding RCT via CER (25% daily energy restriction) or IER (alternating ad libitum and 75% energy restriction days). Probe days were conducted at baseline and post-intervention to assess body composition, ad libitum energy intake and subjective appetite in response to a fixed-energy breakfast, and eating behavior traits. After baseline measurements, participants were allocated to CER (n = 22) or IER (n = 24). Per protocol analyses (≥5% WL within 12 wk) were conducted with use of repeated measures ANOVA. Results Thirty of 37 completers reached ≥5% WL [CER (n = 18): 6.3 ± 0.8% in 57 ± 16 d, IER (n = 12): 6.6 ± 1.1% in 67 ± 13 d; % WL P = 0.43 and days P = 0.10]. Fat mass [−3.9 (95% CI: −4.3, −3.4) kg] and FFM [−1.3 (95% CI: −1.6, −1.0) kg] were reduced post-WL (P &lt; 0.001), with no group differences. Self-selected meal size decreased post-WL in CER (P = 0.03) but not in IER (P = 0.19). Hunger AUC decreased post-WL (P &lt; 0.05), with no group differences. Satiety quotient remained unchanged and was similar in both groups. Both interventions improved dietary restraint, craving control, susceptibility to hunger, and binge eating (P &lt; 0.001). Conclusions Controlled ≥5% WL via CER or IER did not differentially affect changes in body composition, reductions in hunger, and improvements in eating behavior traits. This suggests that neither CER nor IER lead to compensatory adaptations in appetite in women with overweight/obesity. This trial was registered at clinicaltrials.gov as NCT03447600.


2003 ◽  
Vol 88 (4) ◽  
pp. 1577-1586 ◽  
Author(s):  
David S. Weigle ◽  
David E. Cummings ◽  
Patricia D. Newby ◽  
Patricia A. Breen ◽  
R. Scott Frayo ◽  
...  

Loss of body fat by caloric restriction is accompanied by decreased circulating leptin levels, increased ghrelin levels, and increased appetite. In contrast, dietary fat restriction often decreases adiposity without increasing appetite. Substitution of dietary carbohydrate for fat has been shown to increase the area under the plasma leptin vs. time curve (AUC) over the course of 24 h. This effect, if sustained, could explain the absence of a compensatory increase in appetite on a low fat diet. To clarify the effect of dietary fat restriction on leptin and ghrelin, we measured AUC for these hormones in human subjects after each of the following sequential diets: 2 wk on a weight-maintaining 35% fat (F), 45% carbohydrate (C), 20% protein (P) diet (n = 18); 2 wk on an isocaloric 15% F, 65% C, 20% P diet (n = 18); and 12 wk on an ad libitum 15% F, 65% C, 20% P diet (n = 16). AUC for leptin was similar on the isocaloric 15% F and 35% F diets (555 ± 57 vs. 580 ± 56 ng/ml·24 h; P = NS). Body weight decreased from 74.6 ± 2.4 to 70.8 ± 2.7 kg on the ad libitum 15% F diet (P &lt; 0.001) without compensatory increases in food consumption or AUC for ghrelin. Proportional amplitude of the 24-h leptin profile was increased after 12 wk on the 15% fat diet. We conclude that weight loss early in the course of dietary fat restriction occurs independently of increased plasma leptin levels, but that a later increase in amplitude of the 24-h leptin signal may contribute to ongoing weight loss. Fat restriction avoids the increase in ghrelin levels caused by dietary energy restriction.


2009 ◽  
Vol 102 (3) ◽  
pp. 337-341 ◽  
Author(s):  
Taru K. Pilvi ◽  
Saara Harala ◽  
Riitta Korpela ◽  
Eero M. Mervaala

The aim of the study was to compare the effect of different whey protein-containing high-Ca diets on weight loss and weight regain in a model of diet-induced obesity. Obesity was induced in C57BL/6J mice with a high-fat (60 % of energy) diet. Weight loss by energy restriction was performed on four different high-Ca diets (1·8 % CaCO3) containing different whey proteins (18 % of energy): α-lactalbumin (ALA), β-lactoglobulin (BLG), lactoferrin (LF) and whey protein isolate (WPI). After 7 weeks of energy restriction some of the mice were killed and the rest were fed with the same diets ad libitum for 7 weeks. The mice on the LF diet lost significantly more weight than mice on the WPI diet. The body fat content in the ALA and LF groups was significantly lower than in the WPI group (P < 0·05) and the LF group differed significantly even from the BLG group (P < 0·05). Ad libitum feeding after weight loss resulted in weight regain in all groups and only the ALA diet significantly reduced fat accumulation during weight regain. The weight regain was most pronounced in the LF group, but the adipocyte size was still significantly smaller than in the other groups. There were no differences in food intake or apparent fat digestibility between the groups. It can be concluded that a high-Ca diet with ALA significantly improves the outcome of weight loss and subsequent weight regain during the feeding of a high-fat diet in C57BL/6J mice, in comparison with WPI.


2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Isabelle Morin ◽  
Catherine Bégin ◽  
Julie Maltais-Giguère ◽  
Alexandra Bédard ◽  
André Tchernof ◽  
...  

Weight loss has been associated with changes in eating behaviors and appetite sensations that favor a regain in body weight. Since traditional weight loss approaches emphasize the importance of increasing cognitive dietary restraint (CDR) to achieve negative energy imbalance, it is difficult to untangle the respective contributions of energy restriction and increases in CDR on factors that can eventually lead to body weight regain. The present study aimed at comparing the effects of energy restriction alone or in combination with experimentally induced CDR on eating behavior traits, appetite sensations, and markers of stress in overweight and obese women. We hypothesized that the combination of energy restriction and induced CDR would lead to more prevalent food cravings, increased appetite sensations, and higher cortisol concentrations than when energy restriction is not coupled with induced CDR. A total of 60 premenopausal women (mean BMI: 32.0 kg/m2; mean age: 39.4 y) were provided with a low energy density diet corresponding to 85% of their energy needs during a 4-week fully controlled period. At the same time, women were randomized to either a condition inducing an increase in CDR (CDR+ group) or a condition in which CDR was not induced (CRD− group). Eating behavior traits (Three-Factor Eating Questionnaire and Food Craving Questionnaire), appetite sensations (after standardized breakfast), and markers of stress (Perceived Stress Scale; postawakening salivary cortisol) were measured before (T = 0 week) and after (T = 4 weeks) the 4-week energy restriction, as well as 3 months later. There was an increase in CDR in the CDR+ group while no such change was observed in the CDR− group (p=0.0037). No between-group differences were observed for disinhibition, hunger, cravings, appetite sensations, perceived stress, and cortisol concentrations. These results suggest that a slight increase in CDR has no negative impact on factors regulating energy balance in the context of energy restriction.


Circulation ◽  
2017 ◽  
Vol 135 (suppl_1) ◽  
Author(s):  
Christopher D Gardner ◽  
Michelle Hauser ◽  
Liana Del Gobbo ◽  
John Trepanowski ◽  
Joseph Rigdon ◽  
...  

Background: Dietary modification remains an essential component of successful weight loss strategies. No one dietary strategy has been determined to be superior to others for the general population. Studies that contrast reducing dietary fat vs. carbohydrate report consistently high within-group variability in dietary adherence and weight loss. Previous research by our group and others suggest that insulin-glucose dynamics or genotype patterns may modify diet effects. Objective: To determine if within-group weight loss variability on a Healthy Low-Fat (HLF) vs. a Healthy Low Carbohydrate (HLC) diet can be attributed to underlying factors such as insulin-glucose dynamics (i.e., insulin resistance and secretion) or genotype pattern. We hypothesized the above factors would be effect modifiers of HLF and HLC diets on 12-month weight loss. Methods: Generally healthy, non-diabetic adults, 18-50 years, BMI 28-40 kg/m 2 , were randomized to HLF or HLC with no specific prescribed energy restriction for 12 months (n=609). Health educators delivered the intervention in 22 1-hr group classes. Data were collected at 0, 3, 6, & 12 months. Dietary intake was assessed by three 24-hour recalls/time point. Clinical data includes: 75-g glucose oral glucose tolerance tests (insulin concentration at 30 minutes [Ins-30], a measure of insulin secretion), genotyping (3-SNP multilocus genotype: Low-Fat Genotype vs. Low-Carb Genotype, UK Biobank Axiom® array), body composition (DXA), resting energy expenditure (indirect calorimetry), epigenetics, proteomics, subcutaneous adipose tissue, microbiota, and standard CVD risk indicators. Results: At 12 months participants collectively lost 6,559 lbs. Retention was 79%, with equal dropout between arms. Range of weight change in both diet arms was ~80 lbs (-60 to +20 lbs). Macronutrient distribution at 12 months was 48% vs. 30% carbohydrate, 29% vs. 45% fat, and 21% vs. 23% protein for HLF and HLC, respectively. Both groups reported achieving and maintaining an average ~500 kcal deficit relative to baseline. Weight loss was similar for HLF vs. HLC: -12.1 ± 1.1 lbs vs. -13.8 ± 1.0 lbs, mean ± SEM. Neither Ins-30 (p for interaction = 0.84) nor genotype pattern (p for interaction = 0.20) modified the effect of diet on 12-month weight loss. Conclusions: Despite substantial weight loss, high within-group variability, and strong dietary differentiation between groups, neither baseline Ins-30 nor genotype pattern modified the effect of diet on 12-month weight loss. Focus on a healthy diet in both diet arms is novel in the context of many previous Low-Fat vs. Low-Carb studies and may have diminished expected effect modification. The extensive data set collected will be used to explore this and other potential explanatory factors.


QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Ola S Ahmed ◽  
Dalia G Sos ◽  
Dina N. K Boulos ◽  
Samia I El-Damaty ◽  
Maysa A Samy

Abstract Background Obesity is a complex disease involving an excessive amount of body fat. It is a medical problem that increases the risk of heart disease, diabetes, high blood pressure and certain cancers. New evidence supports the view that there is a relationship between consuming energy restricted diet during weight loss program on anthropometric measurements, example; weight, waist circumference, hip circumference and fat percentage. Objectives: to study the effect of weight loss program on anthropometric and laboratory measurements of adult obese females. Method: an intervention study was carried out in the obesity management clinics of National Nutritional institute. Results our findings demonstrate that energy restriction regimen results in modest effect on anthropometric and laboratory measurements which is statistically highly significant. Conclusion and Recommendation: Prevention of obesity should be a high priority in public health, with particular emphasis on encouraging healthy lifestyles in all age groups, starting from early childhood.


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