scholarly journals Characterization of Adult Ghrelin and Ghrelin Receptor Knockout Mice under Positive and Negative Energy Balance

Endocrinology ◽  
2007 ◽  
Vol 149 (2) ◽  
pp. 843-850 ◽  
Author(s):  
Yuxiang Sun ◽  
Nancy F. Butte ◽  
Jose M. Garcia ◽  
Roy G. Smith

Ghrelin and the ghrelin receptor (GH secretagogue receptor, GHS-R), are believed to have important roles in energy homeostasis. We describe results from the first studies to be conducted in congenic (N10) adult ghrelin−/− and Ghsr−/− mice under conditions of both positive (high-fat diet) and negative (caloric restriction) energy balance. In contrast to results from young N2 mutant mice, changes in body weight and energy expenditure are not clearly distinguishable across genotypes. Although respiratory quotient was lower in mice fed a high-fat diet, no differences were evident between littermate wild-type and null genotypes. With normal chow, a modest decrease trend in respiratory quotient was detected in ghrelin−/− mice but not in Ghsr−/− mice. Under caloric restriction, the weight loss of ghrelin−/− and Ghsr−/− mice was identical to wild-type littermates, but blood glucose levels were significantly lower. We conclude that adult congenic ghrelin−/− and Ghsr−/− mice are not resistant to diet-induced obesity but under conditions of negative energy balance show impairment in maintaining glucose homeostasis. These results support our hypothesis that the primary metabolic function of ghrelin in adult mice is to modulate glucose sensing and insulin sensitivity, rather than directly regulate energy intake and energy expenditure.

2018 ◽  
Vol 315 (5) ◽  
pp. G685-G698 ◽  
Author(s):  
Ilya R. Bederman ◽  
Gavriella Pora ◽  
Maureen O’Reilly ◽  
James Poleman ◽  
Kimberly Spoonhower ◽  
...  

Negative energy balance is a prevalent feature of cystic fibrosis (CF). Pancreatic insufficiency, elevated energy expenditure, lung disease, and malnutrition, all characteristic of CF, contribute to the negative energy balance causing low body-growth phenotype. As low body weight and body mass index strongly correlate with poor lung health and survival of patients with CF, improving energy balance is an important clinical goal (e.g., high-fat diet). CF mouse models also exhibit negative energy balance (growth retardation and high energy expenditure), independent from exocrine pancreatic insufficiency, lung disease, and malnutrition. To improve energy balance through increased caloric intake and reduced energy expenditure, we disrupted leptin signaling by crossing the db/db leptin receptor allele with mice carrying the R117H Cftr mutation. Compared with db/db mice, absence of leptin signaling in CF mice (CF db/db) resulted in delayed and moderate hyperphagia with lower de novo lipogenesis and lipid deposition, producing only moderately obese CF mice. Greater body length was found in db/db mice but not in CF db/db, suggesting CF-dependent effect on bone growth. The db/db genotype resulted in lower energy expenditure regardless of Cftr genotype leading to obesity. Despite the db/db genotype, the CF genotype exhibited high respiratory quotient indicating elevated carbohydrate oxidation, thus limiting carbohydrates for lipogenesis. In summary, db/db-linked hyperphagia, elevated lipogenesis, and morbid obesity were partially suppressed by reduced CFTR activity. CF mice still accrued large amounts of adipose tissue in contrast to mice fed a high-fat diet, thus highlighting the importance of dietary carbohydrates and not simply fat for energy balance in CF. NEW & NOTEWORTHY We show that cystic fibrosis (CF) mice are able to accrue fat under conditions of carbohydrate overfeeding, increased lipogenesis, and decreased energy expenditure, although length was unaffected. High-fat diet feeding failed to improve growth in CF mice. Morbid db/db-like obesity was reduced in CF double-mutant mice by reduced CFTR activity.


2021 ◽  
Author(s):  
Patrick Mullie ◽  
Pieter Maes ◽  
Laurens van Veelen ◽  
Damien Van Tiggelen ◽  
Peter Clarys

ABSTRACT Introduction Adequate energy supply is a prerequisite for optimal performances and recovery. The aims of the present study were to estimate energy balance and energy availability during a selection course for Belgian paratroopers. Methods Energy expenditure by physical activity was measured with accelerometer (ActiGraph GT3X+, ActiGraph LLC, Pensacola, FL, USA) and rest metabolic rate in Cal.d−1 with Tinsley et al.’s equation based on fat-free mass = 25.9 × fat-free mass in kg + 284. Participants had only access to the French individual combat rations of 3,600 Cal.d−1, and body fat mass was measured with quadripolar impedance (Omron BF508, Omron, Osaka, Japan). Energy availability was calculated by the formula: ([energy intake in foods and beverages] − [energy expenditure physical activity])/kg FFM−1.d−1, with FFM = fat-free mass. Results Mean (SD) age of the 35 participants was 25.1 (4.18) years, and mean (SD) percentage fat mass was 12.0% (3.82). Mean (SD) total energy expenditure, i.e., the sum of rest metabolic rate, dietary-induced thermogenesis, and physical activity, was 5,262 Cal.d−1 (621.2), with percentile 25 at 4,791 Cal.d−1 and percentile 75 at 5,647 Cal.d−1, a difference of 856 Cal.d−1. Mean daily energy intake was 3,600 Cal.d−1, giving a negative energy balance of 1,662 (621.2) Cal.d−1. Mean energy availability was 9.3 Cal.kg FFM−1.d−1. Eleven of the 35 participants performed with a negative energy balance of 2,000 Cal.d−1, and only five participants out of 35 participants performed at a less than 1,000 Cal.d−1 negative energy balance level. Conclusions Energy intake is not optimal as indicated by the negative energy balance and the low energy availability, which means that the participants to this selection course had to perform in suboptimal conditions.


1998 ◽  
Vol 10 (1) ◽  
pp. 65 ◽  
Author(s):  
Stephen J. Judd

Animal reproduction is impaired when intake of energy is so restricted that activities essential to life are threatened; this is seen as a homeostatic adjustment that restricts wasteful energy expenditure. Fasting or exercising to a degree requiring considerable energy expenditure has major effects on the hypothalamus, including activation of corticotrophin-releasing factor (CRF) neurons, suppression of thyrotrophin-releasing hormone synthesis, and increased growth hormone secretion; these are associated with increased concentrations of hypothalamic neuropeptide Y mRNA and are corrected by administration of leptin, an adipose-tissue protein with a tertiary structure similar to the cytokine interleukin-2. This response to fasting results from a disordered pattern of activity in the gonadotrophin-releasing hormone (GnRH) pacemaker, characterized by reduced luteinizing hormone pulsatility, particularly during daytime. Animal studies have suggested that the response depends on an intact afferent vagal system from the stomach and the presence of oestrogen. Noradrenergic neurons forming the A2 group increase the activity of CRF neurons that, in turn, inhibit GnRH pulsatility. Reproductive impairment due to fasting is reversed by leptin, and abnormalities of leptin are described in individuals who fast or who develop exercise-induced amenorrhoea. This paper discusses these changes induced by negative energy balance and speculates on the involvement of leptin as a contributor to these abnormalities.


2020 ◽  
Vol 8 (4_suppl3) ◽  
pp. 2325967120S0020
Author(s):  
Julie A. Young ◽  
Jessica Napolitano ◽  
Mitchell J. Rauh ◽  
Jeanne Nichols ◽  
Anastasia N. Fischer

BACKGROUND: Prior studies have shown that vital signs such as heart rate, blood pressure and body temperature are depressed in patients with an eating disorder who have experienced a negative energy balance for a significant amount of time. More recently, a negative energy balance has been the focus of Relative Energy Deficiency in Sport (RED-S), which links energy availability to the health of multiple body systems in adults in as little as 5 days with a negative energy balance. High rates of disordered eating patterns have been reported in high school athletes. As adolescents grow, the consequences of a negative energy balance can be significant and potentially irreversible. Thus, vital signs may help clinicians quickly evaluate a patient’s energy status or highlight them for further evaluation. PURPOSE: The purpose of this study was to examine energy balance and vital signs in a cohort of adolescents who were seen by a sports dietitian to gain weight or optimize sports performance. METHODS: We evaluated 240 subjects, 83% female, average age 15.0±2.3 years. Heart rate and blood pressure were measured with a dynamometer in a seated position. Body temperature was measured orally. Height and weight were recorded. BMI was then calculated and evaluated by percentile. Energy intake was assessed using a 3-day food recall log. Energy expenditure was calculated using Harris Benedict Equation and combined with estimated exercise energy expenditure. Energy balance was estimated as energy intake minus energy expenditure. RESULTS: Average age was 15.03±2.71. 85% were female. 30% were below the 15th percentile for BMI. There were no differences in BMI percentiles between males and females (p=0.99). The average heart rate was 71.62±13.4 bpm and 19% were below the 10th percentile for heart rate. Average systolic blood pressure was 110±11 mm Hg and average diastolic blood pressure was 62±7 mmHg. Average temperature was 98.1±.4 degrees F. 88%were in a negative energy balance with an average energy deficit of 552±511 calories. There were no statistically significant differences in energy balance between males and females (p=0.08). CONCLUSIONS: A disproportional number of children with low BMI and heart rate percentiles was observed, which may indicate a long-standing energy deficiency. We also found a high proportion of adolescents who experienced a standalone negative energy balance itself or vital signs consistent with a negative energy balance. Additional studies are needed to study the relationships between energy deficit magnitude and duration in adolescents and children.


2004 ◽  
Vol 24 (7) ◽  
pp. 2978-2985 ◽  
Author(s):  
J. G. Hohmann ◽  
D. N. Teklemichael ◽  
D. Weinshenker ◽  
D. Wynick ◽  
D. K. Clifton ◽  
...  

ABSTRACT Neuropeptide Y (NPY) and galanin have both been implicated in the regulation of body weight, yet mice bearing deletions of either of these molecules have unremarkable metabolic phenotypes. To investigate whether galanin and NPY might compensate for one another, we produced mutants lacking both neuropeptides (GAL−/−/NPY−/−). We found that male GAL−/−/NPY−/− mice ate significantly more and were much heavier (30%) than wild-type (WT) controls. GAL−/−/NPY−/− mice responded to a high-fat diet by gaining more weight than WT mice gain, and they were unable to regulate their weight normally after a change in diet. GAL−/−/NPY−/− mice had elevated levels of leptin, insulin, and glucose, and they lost more weight than WT mice during chronic leptin treatment. Galanin mRNA was increased in the hypothalamus of NPY−/− mice, providing evidence of compensatory regulation in single mutants. The disruption of energy balance observed in GAL−/−/NPY−/− double knockouts is not found in the phenotype of single knockouts of either molecule. The unexpected obesity phenotype may result from the dysregulation of the leptin and insulin systems that normally keep body weight within the homeostatic range.


Endocrinology ◽  
2016 ◽  
Vol 157 (4) ◽  
pp. 1457-1466 ◽  
Author(s):  
Miyuki Shibata ◽  
Ryoichi Banno ◽  
Mariko Sugiyama ◽  
Takashi Tominaga ◽  
Takeshi Onoue ◽  
...  

Abstract Agouti-related protein (AgRP) expressed in the arcuate nucleus is a potent orexigenic neuropeptide, which increases food intake and reduces energy expenditure resulting in increases in body weight (BW). Glucocorticoids, key hormones that regulate energy balance, have been shown in rodents to regulate the expression of AgRP. In this study, we generated AgRP-specific glucocorticoid receptor (GR)-deficient (knockout [KO]) mice. Female and male KO mice on a high-fat diet (HFD) showed decreases in BW at the age of 6 weeks compared with wild-type mice, and the differences remained significant until 16 weeks old. The degree of resistance to diet-induced obesity was more robust in female than in male mice. On a chow diet, the female KO mice showed slightly but significantly attenuated weight gain compared with wild-type mice after 11 weeks, whereas there were no significant differences in BW in males between genotypes. Visceral fat pad mass was significantly decreased in female KO mice on HFD, whereas there were no significant differences in lean body mass between genotypes. Although food intake was similar between genotypes, oxygen consumption was significantly increased in female KO mice on HFD. In addition, the uncoupling protein-1 expression in the brown adipose tissues was increased in KO mice. These data demonstrate that the absence of GR signaling in AgRP neurons resulted in increases in energy expenditure accompanied by decreases in adiposity in mice fed HFD, indicating that GR signaling in AgRP neurons suppresses energy expenditure under HFD conditions.


1997 ◽  
Vol 136 (3) ◽  
pp. 309-315 ◽  
Author(s):  
Susanna Iossa ◽  
Maria Pina Mollica ◽  
Lillà Lionetti ◽  
Antonio Barletta ◽  
Giovanna Liverini

Abstract We have carried out measurements of energy balance in hypothyroid rats fed a low-fat or a high-fat diet for eighteen days. We have also measured cephalic and processing thermic effect of food (TEF) after a low-fat or a high-fat meal. Body lipid gain, carcass lipid content and gross efficiency were significantly (P < 0·05) higher in hypothyroid rats fed a high-fat diet compared with hypothyroid rats fed a low-fat diet, while metabolizable energy intake and energy expenditure remained unchanged. Cephalic TEF after a low-fat meal was significantly (P < 005) lower in hypothyroid rats fed a high-fat diet compared with hypothyroid rats fed a low-fat diet, while it was significantly (P <0·05) higher after a high-fat meal than after a low-fat meal in hypothyroid rats fed a high-fat diet. No significant variation was found in processing TEF after a low-fat or a high-fat meal. Our results indicate that hypothyroid rats are unable to develop increased energy expenditure and increased TEF in response to a high-fat diet. European Journal of Endocrinology 136 309–315


Endocrinology ◽  
2011 ◽  
Vol 152 (1) ◽  
pp. 48-58 ◽  
Author(s):  
Andrew J. Hoy ◽  
Clinton R. Bruce ◽  
Sarah M. Turpin ◽  
Alexander J. Morris ◽  
Mark A. Febbraio ◽  
...  

Abstract Adipose triglyceride lipase (ATGL) null (−/−) mice store vast amounts of triacylglycerol in key glucoregulatory tissues yet exhibit enhanced insulin sensitivity and glucose tolerance. The mechanisms underpinning these divergent observations are unknown but may relate to the reduced availability of circulating fatty acids. The aim of this study was to determine whether the enhancements in insulin stimulated glucose metabolism in ATGL−/− mice persist when challenged with a high-fat diet. ATGL−/− mice fed a low-fat diet exhibit improved whole-body insulin sensitivity and glucose tolerance compared with wild-type mice. Wild-type mice became hyperlipidemic and insulin-resistant when challenged with a high-fat diet (HFD, 60% fat) for 4 wk. ATGL−/− mice fed a HFD had elevated circulating fatty acids but had reduced fasting glycemia compared to pre–high-fat diet levels and were refractory to glucose intolerance and insulin resistance. This protection from high-fat diet–induced metabolic perturbations was associated with a preference for fatty acid utilization but reduced energy expenditure and no change in markers of mitochondrial capacity or density. The protection from high-fat diet–induced insulin resistance in ATGL−/− mice was due to increased cardiac and liver insulin-stimulated glucose clearance despite increased lipid content in these tissues. Additionally, there was no difference in skeletal muscle insulin-stimulated glucose disposal, but there was a reduction observed in brown adipose tissue. Overall, these results show that ATGL−/− mice are protected from HFD-induced insulin resistance and reveal a tissue specific disparity between lipid accumulation and insulin sensitivity.


PLoS ONE ◽  
2013 ◽  
Vol 8 (7) ◽  
pp. e67786 ◽  
Author(s):  
Pilou L. H. R. Janssens ◽  
Rick Hursel ◽  
Eveline A. P. Martens ◽  
Margriet S. Westerterp-Plantenga

1999 ◽  
Vol 276 (6) ◽  
pp. R1739-R1748 ◽  
Author(s):  
T. P. Stein ◽  
M. J. Leskiw ◽  
M. D. Schluter ◽  
R. W. Hoyt ◽  
H. W. Lane ◽  
...  

The objectives of this study were as follows: 1) to measure human energy expenditure (EE) during spaceflight on a shuttle mission by using the doubly labeled water (DLW) method; 2) to determine whether the astronauts were in negative energy balance during spaceflight; 3) to use the comparison of change in body fat as measured by the intake DLW EE,18O dilution, and dual energy X-ray absorptiometry (DEXA) to validate the DLW method for spaceflight; and 4) to compare EE during spaceflight against that found with bed rest. Two experiments were conducted: a flight experiment ( n = 4) on the 16-day 1996 life and microgravity sciences shuttle mission and a 6° head-down tilt bed rest study with controlled dietary intake ( n = 8). The bed rest study was designed to simulate the flight experiment and included exercise. Two EE determinations were done before flight (bed rest), during flight (bed rest), and after flight (recovery). Energy intake and N balance were monitored for the entire period. Results were that body weight, water, fat, and energy balance were unchanged with bed rest. For the flight experiment, decreases in weight (2.6 ± 0.4 kg, P < 0.05) and N retention (−2.37 ± 0.45 g N/day, P < 0.05) were found. Dietary intake for the four astronauts was reduced in flight (3,025 ± 180 vs. 1,943 ± 179 kcal/day, P < 0.05). EE in flight was 3,320 ± 155 kcal/day, resulting in a negative energy balance of 1,355 ± 80 kcal/day (−15.7 ± 1.0 kcal ⋅ kg−1 ⋅ day−1, P < 0.05). This corresponded to a loss of 2.1 ± 0.4 kg body fat, which was within experimental error of the fat loss determined by18O dilution (−1.4 ± 0.5 kg) and DEXA (−2.4 ± 0.4 kg). All three methods showed no change in body fat with bed rest. In conclusion, 1) the DLW method for measuring EE during spaceflight is valid, 2) the astronauts were in severe negative energy balance and oxidized body fat, and 3) in-flight energy (E) requirements can be predicted from the equation: E = 1.40 × resting metabolic rate + exercise.


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