scholarly journals Activation of the central melanocortin system chronically reduces body mass without the necessity of long-term caloric restriction

2017 ◽  
Vol 95 (2) ◽  
pp. 206-214 ◽  
Author(s):  
I. Côté ◽  
Y. Sakarya ◽  
N. Kirichenko ◽  
D. Morgan ◽  
C.S. Carter ◽  
...  

Melanotan II (MTII) is a potent appetite suppressor that rapidly reduces body mass. Given the rapid loss of anorexic response upon chronic MTII treatment, most investigations have focused on the initial physiological adaptations. However, other evidence supports MTII as a long-term modulator of energy balance that remains to be established. Therefore, we examined the chronic effects of MTII on energy homeostasis. MTII (high or low dose) or artificial cerebrospinal fluid (aCSF) was infused into the lateral ventricle of the brain of 6-month-old F344BN rats (6–7/group) over 40 days. MTII suppressed appetite in a dose-dependent manner (P < 0.05). Although food intake promptly rose back to control level, body mass was persistently reduced in both MTII groups (P < 0.01). At day 40, both MTII groups displayed lower adiposity than the aCSF animals (P < 0.01). These results show that MTII chronically reduces body mass without the requirement of long-term caloric restriction. Our study proposes that food restriction helps initiate mass loss; however, combined with a secondary pharmacological approach preserving a negative energy balance state over time may help combat obesity.

2018 ◽  
Vol 239 (1) ◽  
pp. 19-31 ◽  
Author(s):  
K Eerola ◽  
S Virtanen ◽  
L Vähätalo ◽  
L Ailanen ◽  
M Cai ◽  
...  

γ-Melanocyte stimulating hormone (γ-MSH) is an endogenous agonist of the melanocortin 3-receptor (MC3R). Genetic disruption of MC3Rs increases adiposity and blunts responses to fasting, suggesting that increased MC3R signaling could be physiologically beneficial in the long term. Interestingly, several studies have concluded that activation of MC3Rs is orexigenic in the short term. Therefore, we aimed to examine the short- and long-term effects of γ-MSH in the hypothalamic arcuate nucleus (ARC) on energy homeostasis and hypothesized that the effect of MC3R agonism is dependent on the state of energy balance and nutrition. Lentiviral gene delivery was used to induce a continuous expression of γ-Msh only in the ARC of male C57Bl/6N mice. Parameters of body energy homeostasis were monitored as food was changed from chow (6 weeks) to Western diet (13 weeks) and back to chow (7 weeks). The γ-MSH treatment decreased the fat mass to lean mass ratio on chow, but the effect was attenuated on Western diet. After the switch back to chow, an enhanced loss in weight (−15% vs −6%) and fat mass (−37% vs −12%) and reduced cumulative food intake were observed in γ-MSH-treated animals. Fasting-induced feeding was increased on chow diet only; however, voluntary running wheel activity on Western diet was increased. The γ-MSH treatment also modulated the expression of key neuropeptides in the ARC favoring weight loss. We have shown that a chronic treatment intended to target ARC MC3Rs modulates energy balance in nutritional state-dependent manner. Enhancement of diet-induced weight loss could be beneficial in treatment of obesity.


2018 ◽  
Vol 96 (3) ◽  
pp. 308-312 ◽  
Author(s):  
Isabelle Côté ◽  
Sara M. Green ◽  
Drake Morgan ◽  
Christy S. Carter ◽  
Nihal Tümer ◽  
...  

Recent evidence indicate that melanotan II (MTII) reduces body mass independently of caloric reduction. Because MTII induces a transient hypophagia, caloric reduction is still considered a primary mechanism for MTII-mediated body mass loss. To examine the contribution of caloric reduction to long-term body mass loss in response to MTII, we centrally infused MTII or vehicle in ad libitum fed (MTII and Control) animals in comparison with a group of animals that were pair-fed (PF) to the MTII group. Food intake and body mass were recorded daily, and body composition was assessed biweekly. The present study demonstrates that central MTII-mediated body mass loss is only partially mediated by caloric restriction, and the long-term body mass loss is independent of the initial hypophagia. More importantly, central MTII administration induced a rapid but sustained fat mass loss, independently of caloric reduction. MTII-treated animals preserved their lean/fat mass ratio throughout the study, whereas PF animals underwent a transient reduction of lean/fat mass ratio that was only normalized when food intake returned to Control level. In summary, it can be concluded that activation of the central melanocortin system in rats persistently reduces body and fat mass independently of caloric reduction.


2018 ◽  
Vol 72 (4) ◽  
pp. 279-286 ◽  
Author(s):  
Ana Claudia Pelissari Kravchychyn ◽  
Raquel Munhoz da Silveira Campos ◽  
Flávia Campos Corgosinho ◽  
Deborah Cristina Landi Masquio ◽  
Sofia Emanuelle de Castro Ferreira Vicente ◽  
...  

Background: Deregulation of orexigenic and anorexigenic pathways occurs among adolescents with obesity. Alpha-melanocyte-stimulating hormone (α-MSH) is a key catabolic mediator of energy homeostasis and an important anorexigenic neuropeptide in the control of energy balance and thermogenesis. However, it was not well explored if α-MSH can modulate long-term weight loss therapy responses in a dependent manner according to its concentration. Our hypothesis is that a high α-MSH concentration at baseline promotes better modulation of anorexigenic/orexigenic pathways in obese adolescents. Methods: One hundred ten post-pubertal obese adolescents (body mass index >95th percentile) were submitted to 1 year of interdisciplinary therapy (clinical, nutritional, psychological, physical exercise, and physiotherapy support). Body composition and plasma levels of α-MSH, neuropeptide Y (NPY), melanin-concentrating hormone, and agouti-related peptide (AgRP) were measured before and after therapy. The volunteers were grouped on the basis of Tertiles of α-MSH concentration: Low (<0.75 ng/mL), Medium (≤0.76 to ≥1.57 ng/mL), and High (>1.57 ng/mL). Significance was set as p < 0.05. Results: The treatment promoted a significant improvement in body adiposity and fat free mass for all groups. It is important to note that only in the high α-MSH group, a significant increase of the α-MSH/NPY ratio and decrease NPY/AgRP ratio post treatment were observed. Conclusion: The high α-MSH concentration promotes better modulation of anorexigenic/orexigenic pathways in obese adolescents following long-term weight loss therapy and this is important in clinical practice.


Endocrinology ◽  
2003 ◽  
Vol 144 (3) ◽  
pp. 760-766 ◽  
Author(s):  
Lynn E. Pritchard ◽  
Robert L. Oliver ◽  
Julie D. McLoughlin ◽  
Susan Birtles ◽  
Catherine B. Lawrence ◽  
...  

Regulation of proopiomelanocortin (POMC) is an important means of controlling the central melanocortin system. It has never been established whether the spectrum of POMC-derived peptides synthesized and secreted from the hypothalamus is altered in response to changes in energy homeostasis in vivo. To monitor secretion, we analyzed peptide content of rat cerebrospinal fluid. Strikingly, both the POMC precursor and ACTH were readily detected. Moreover, levels of both were lower in samples from obese Zucker rats (fa/fa) vs. lean Zucker rats (+/+, fa/+) and from fasted vs. fed rats, whereas αMSH could not be detected. POMC levels were also decreased in hypothalamic extracts from obese and fasted animals. In contrast, despite being the most predominant peptide in extracts, αMSH levels weren’t significantly changed in any of the rat models. The ratio of precursor to derived peptides in cerebrospinal fluid was significantly higher in obese vs. lean and fed vs. fasted rats, indicating that secretion of POMC-derived peptides is differentially down-regulated during negative energy balance. In contrast to peptide analysis, we found that POMC gene expression was not significantly decreased in fasted rat hypothalami. We conclude that regulation of peptide secretion is an important mechanism by which the POMC system is controlled.


Nutrients ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 1814 ◽  
Author(s):  
Yu Chooi ◽  
Cherlyn Ding ◽  
Zhiling Chan ◽  
Jezebel Lo ◽  
John Choo ◽  
...  

Weight loss, induced by chronic energy deficit, improves the blood lipid profile. However, the effects of an acute negative energy balance and the comparative efficacy of diet and exercise are not well-established. We determined the effects of progressive, acute energy deficits (20% or 40% of daily energy requirements) induced by a single day of calorie restriction (n = 19) or aerobic exercise (n = 13) in healthy subjects (age: 26 ± 9 years; body mass index (BMI): 21.8 ± 2.9 kg/m2). Fasting plasma concentrations of very low-, intermediate-, low-, and high-density lipoprotein (VLDL, LDL, IDL, and HDL, respectively) particles and their subclasses were determined using nuclear magnetic resonance. Total plasma triglyceride and VLDL-triglyceride concentrations decreased after calorie restriction and exercise (all p ≤ 0.025); the pattern of change was linear with an increasing energy deficit (all p < 0.03), with no evidence of plateauing. The number of circulating large and medium VLDL particles decreased after diet and exercise (all p < 0.015), with no change in small VLDL particles. The concentrations of IDL, LDL, and HDL particles, their relative distributions, and the particle sizes were not altered. Our data indicate that an acute negative energy balance induced by calorie restriction and aerobic exercise reduces triglyceride concentrations in a dose-dependent manner, by decreasing circulating large and medium VLDL particles.


2009 ◽  
Vol 57 (1) ◽  
pp. 139-146
Author(s):  
Andrea Győrffy ◽  
Mónika Keresztes ◽  
Vera Faigl ◽  
Vilmos Frenyó ◽  
Margit Kulcsár ◽  
...  

In the regulation of energy metabolism, the liver plays an important role in the reinforcement of energy production. In periparturient cows the energy homeostasis turns into a negative energy balance that may shift the physiological regulation of energy balance towards pathological processes. Propylene glycol (PG), as a complementary source of energy used in the nutrition of dairy cows, alters systemic thyroid hormone economy; however, the exact mechanism through which highly glycogenic feed supplements impact liver metabolism is little known. Previous studies showed that only leptin receptors are expressed in the liver of cows, and now we report that leptin mRNA is expressed in the liver of cows as well. The present results show that the mRNA of leptin and its receptors are differentially modulated by the increased energy content of the feed consumed. Simultaneous changes in hepatic type I deiodinase activity suggest that hepatic modulation of the leptin system by PG supplementation may be mediated by an increased local thyroxine-triiodothyronine conversion. Since PG supplementation with simultaneous T4–T3 turnover and increased hepatic leptin- and short-form leptin receptor mRNA were not associated with a significant change in hepatic total lipid levels, it is suggested that the leptin system, directly or indirectly modulated by thyroid hormones, may represent a local defence mechanism to prevent fatty liver formation.


Sports ◽  
2018 ◽  
Vol 6 (3) ◽  
pp. 82 ◽  
Author(s):  
Majid Syed-Abdul ◽  
Dhwani Soni ◽  
Jason Wagganer

Low caloric intake or excessive energy expenditure can lead to a negative energy balance, which, in female athletes, may result in a condition called the female athlete triad. While several guidelines identified proper nutrition as a first line of treatment, little research has been reported to show the effect of a professional nutrition program (PNP) on the female athlete triad. The purpose of this case report was to measure the short- and long-term effects of a PNP on a female athlete presenting triad characteristics. A 20-year-old female track-and-field athlete at a Division I university who was in negative energy balance and amenorrheic underwent a one-month PNP. Short- and long-term effects measured by a dual X-ray absorptiometry scan prior to and after attending a PNP showed increased total energy intake from 2188 kcals to 3187 kcals, which resulted in an increase in body fat percent (BF%) from 4.7% to 6.7%. However, by the end of four months, energy intake and BF% (5.7% and 6.0%) values were reduced, respectively. After the twelve-month follow-up, BF% was increased (10.5%), suggesting that increasing energy intake to meet energy demands, without compromising athletic training, can be an effective treatment for the female athlete triad.


Endocrinology ◽  
2006 ◽  
Vol 147 (7) ◽  
pp. 3190-3195 ◽  
Author(s):  
Kate L. J. Ellacott ◽  
Ilia G. Halatchev ◽  
Roger D. Cone

The central melanocortin system plays a key role in the regulation of energy homeostasis. Neurons containing the peptide precursor proopiomelanocortin (POMC) are found at two sites in the brain, the arcuate nucleus of the hypothalamus (ARC) and the caudal region of the nucleus of the solitary tract (NTS). ARC POMC neurons, which also express cocaine- and amphetamine-regulated transcript (CART), are known to mediate part of the response to factors regulating energy homeostasis, such as leptin and ghrelin. In contrast, the physiological role(s) of the POMC neurons in the caudal brainstem are not well characterized. However, development of a transgenic mouse expressing green fluorescent protein under the control of the POMC promoter [POMC-enhanced green fluorescent protein (EGFP) mouse] has aided the study of these neurons. Indeed, recent studies have shown significant activation of NTS POMC-EGFP cells by the gut released satiety factor cholecystokinin (CCK). Here we show that peripheral leptin administration induces the expression of phospho-signal transducer and activator of transcription 3 immunoreactivity (pSTAT3-IR), a marker of leptin receptor signaling, in more than 50% of NTS POMC-EGFP neurons. Furthermore, these POMC-EGFP neurons comprise 30% of all pSTAT3-IR cells in the NTS. Additionally, we also show that in contrast to the ARC population, NTS POMC-EGFP neurons do not coexpress CART immunoreactivity. These data suggest that NTS POMC neurons may participate with ARC POMC cells in mediating some of the effects of leptin and thus comprise a novel cell group regulated by both long-term adipostatic signals and satiety factors such as CCK.


2013 ◽  
Vol 38 (4) ◽  
pp. 396-400 ◽  
Author(s):  
Lee M. Margolis ◽  
Jennifer Rood ◽  
Catherine Champagne ◽  
Andrew J. Young ◽  
John W. Castellani

Small Unit Tactics (SUT) is a 64-day phase of the Special Forces Qualification Course designed to simulate real-world combat operations. Assessing the metabolic and physiological responses of such intense training allows greater insights into nutritional requirements of soldiers during combat. The purpose of this study was to examine energy balance around specific training events, as well as changes in body mass and composition. Data were collected from 4 groups of soldiers (n = 36) across 10-day periods. Participants were 28 ± 5 years old, 177 ± 6 cm tall, and weighed 83 ± 7 kg. Doubly labeled water (D218O) was used to assess energy expenditure. Energy intake was calculated by subtracting energy in uneaten foods from known energy in distributed foods in individually packaged combat rations or in the dining facility. Body composition was estimated from skinfold thickness measurements on days 0 and 64 of the course. Simulated urban combat elicited that largest energy deficit (11.3 ± 2.3 MJ·day−1 (2700 ± 550 kcal·day−1); p < 0.05), and reduction in body mass (3.3 ± 1.9 kg; p < 0.05), during SUT, while energy balance was maintained during weapons familiarization training and platoon size raids. Over the entire course body mass decreased by 4.2 ± 3.7 kg (p < 0.01), with fat mass decreasing by 2.8 ± 2.0 kg (p < 0.01) and fat-free mass decreasing by 1.4 ± 2.8 kg (p < 0.05). The overall reduction in body mass suggests that soldiers were in a negative energy balance during SUT, with high energy deficit being observed during strenuous field training.


2021 ◽  
Vol 4 (5) ◽  
pp. 130-141
Author(s):  
Mylena Garcia Proto ◽  
◽  
Milena Cristina Bernardo de Barros ◽  
Bruna Stanigher Barbosa ◽  
◽  
...  

With the increased production demand in the dairy industry comes the need to keep animals healthier, thus avoiding large economic losses due to low productivity. During the transition period, dairy cows are susceptible to the onset of infectious diseases and metabolic imbalances due to the big change in their diet, it could be poor in needed nutrients to maintain the animal's body score, with this, the dry matter intake decreases up to 40% while energy expenditure increases due to milk and colostrum production, getting into a negative energy balance state.


Sign in / Sign up

Export Citation Format

Share Document