Cocaine- and Amphetamine-Regulated Transcript Is a Potent Stimulator of GnRH and Kisspeptin Cells and May Contribute to Negative Energy Balance-induced Reproductive Inhibition in Females

Abstract Cocaine- and amphetamine-regulated transcript (CART) is a hypothalamic neuropeptide implicated in both metabolic and reproductive regulation, raising the possibility that CART plays a role in reproductive inhibition during negative metabolic conditions. The current study characterized CART's regulatory influence on GnRH and kisspeptin (Kiss1) cells and determined the sensitivity of different CART populations to negative energy balance. CART fibers made close appositions to 60% of GnRH cells, with the majority of the fibers (>80%) originating from the arcuate nucleus (ARH) CART/pro-opiomelanocortin population. Electrophysiological recordings in GnRH-green fluorescent protein rats demonstrated that CART postsynaptically depolarizes GnRH cells. CART fibers from the ARH were also observed in close contact with Kiss1 cells in the ARH and anteroventral periventricular nucleus (AVPV). Recordings in Kiss1-GFP mice demonstrated CART also postsynaptically depolarizes ARH Kiss1 cells, suggesting CART may act directly and indirectly, via Kiss1 populations, to stimulate GnRH neurons. CART protein and mRNA levels were analyzed in 2 models of negative energy balance: caloric restriction (CR) and lactation. Both CART mRNA levels and the number of CART-immunoreactive cells were suppressed in the ARH during CR but not during lactation. AVPV CART mRNA was suppressed during CR, but not during lactation when there was a dramatic increase in CART-immunoreactive cells. These data suggest differing regulatory signals of CART between the models. In conclusion, both morphological and electrophysiological methods identify CART as a novel and potent stimulator of Kiss1 and GnRH neurons and suppression of CART expression during negative metabolic conditions could contribute to inhibition of the reproductive axis.

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Orexin activation precedes increased NPY expression, hyperphagia, and metabolic changes in response to sleep deprivation

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00660.2009 ◽

2010 ◽

Vol 298 (3) ◽

pp. E726-E734 ◽

Cited By ~ 60

Author(s):

Paulo José Forcina Martins ◽

Marina Soares Marques ◽

Sergio Tufik ◽

Vânia D'Almeida

Keyword(s):

Body Weight ◽

Energy Balance ◽

Food Intake ◽

Sleep Deprivation ◽

Weight Control ◽

Time Course ◽

Energy Homeostasis ◽

Negative Energy ◽

Negative Energy Balance ◽

Mrna Levels

Several pieces of evidence support that sleep duration plays a role in body weight control. Nevertheless, it has been assumed that, after the identification of orexins (hypocretins), the molecular basis of the interaction between sleep and energy homeostasis has been provided. However, no study has verified the relationship between neuropeptide Y (NPY) and orexin changes during hyperphagia induced by sleep deprivation. In the current study we aimed to establish the time course of changes in metabolite, endocrine, and hypothalamic neuropeptide expression of Wistar rats sleep deprived by the platform method for a distinct period (from 24 to 96 h) or sleep restricted for 21 days (SR-21d). Despite changes in the stress hormones, we found no changes in food intake and body weight in the SR-21d group. However, sleep-deprived rats had a 25–35% increase in their food intake from 72 h accompanied by slight weight loss. Such changes were associated with increased hypothalamus mRNA levels of prepro-orexin (PPO) at 24 h followed by NPY at 48 h of sleep deprivation. Conversely, sleep recovery reduced the expression of both PPO and NPY, which rapidly brought the animals to a hypophagic condition. Our data also support that sleep deprivation rapidly increases energy expenditure and therefore leads to a negative energy balance and a reduction in liver glycogen and serum triacylglycerol levels despite the hyperphagia. Interestingly, such changes were associated with increased serum levels of glucagon, corticosterone, and norepinephrine, but no effects on leptin, insulin, or ghrelin were observed. In conclusion, orexin activation accounts for the myriad changes induced by sleep deprivation, especially the hyperphagia induced under stress and a negative energy balance.

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Insulin restores GH responsiveness during lactation-induced negative energy balance in dairy cattle: effects on expression of IGF-I and GH receptor 1A

Journal of Endocrinology ◽

10.1677/joe.0.1760205 ◽

2003 ◽

Vol 176 (2) ◽

pp. 205-217 ◽

Cited By ~ 172

Author(s):

ST Butler ◽

AL Marr ◽

SH Pelton ◽

RP Radcliff ◽

MC Lucy ◽

...

Keyword(s):

Adipose Tissue ◽

Blood Glucose ◽

Energy Balance ◽

Dairy Cattle ◽

Negative Energy ◽

Negative Energy Balance ◽

Mrna Levels ◽

Hepatic Expression ◽

Gh Receptor ◽

Igf I

Early lactation in dairy cattle is a period of severe negative energy balance (NEB) characterized by reduced blood glucose and insulin concentrations and elevated blood GH concentrations. The liver is refractory to GH during NEB and this uncoupling of the GH-IGF axis results in diminished plasma concentrations of IGF-I. Our objectives were to examine the effects of insulin administration during the immediate postpartum period on plasma IGF-I and GH concentrations and to examine the hepatic expression of total GH receptors (all GH receptor transcripts), GH receptor 1A (GHR 1A) and IGF-I. In addition, we examined adipose tissue for total GH receptor and IGF-I mRNA levels to establish the effects of chronic hyperinsulinemia on an insulin-responsive peripheral tissue. Holstein cows (n=14) were subjected to either a hyperinsulinemic-euglycemic clamp (insulin; INS) or saline infusion (control; CTL) for 96 h starting on day 10 postpartum. Insulin was infused i.v. (1 micro g/kg body weight per h), blood samples were collected hourly, and euglycemia was maintained by infusion of glucose. Insulin concentrations during the infusions were increased 8-fold in INS compared with CTL cows (2.33+/-0.14 vs 0.27+/-0.14 ng/ml (S.E.M.); P<0.001) while blood glucose concentrations were not different between treatments (45.3+/-2.2 vs 42.5+/-2.2 mg/dl; P>0.1). Plasma IGF-I increased continuously during the insulin infusion, and reached the highest concentrations at the end of the clamp, being almost 4-fold higher in INS compared with CTL cows (117+/-4 vs 30+/-4 ng/ml; P<0.001). Hepatic expression of GHR 1A and IGF-I mRNA was low in CTL cows, but was increased 3.6-fold (P<0.05) and 6.3-fold (P<0.001) respectively in INS cows. By contrast, in adipose tissue the changes in gene expression in response to insulin were reversed with decreases in both total GHR and IGF-I mRNA. The expressions of GHR 1A and IGF-I mRNA in liver tissue were correlated in INS (r=0.86; P<0.05), but not CTL cows (r=0.43; P>0.1). Insulin appears to be a key metabolic signal in coupling the GH-IGF axis, thus orchestrating a marked elevation in circulating IGF-I concentrations.

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Leptin Modulates the Response of Brown Adipose Tissue to Negative Energy Balance: Implication of the GH/IGF-I Axis

International Journal of Molecular Sciences ◽

10.3390/ijms22062827 ◽

2021 ◽

Vol 22 (6) ◽

pp. 2827

Author(s):

Vicente Barrios ◽

Laura M. Frago ◽

Sandra Canelles ◽

Santiago Guerra-Cantera ◽

Eduardo Arilla-Ferreiro ◽

...

Keyword(s):

Adipose Tissue ◽

Energy Balance ◽

Brown Adipose Tissue ◽

Uncoupling Protein ◽

Negative Energy ◽

Negative Energy Balance ◽

Cytokine Signaling ◽

Mrna Levels ◽

Brown Adipose ◽

Igf I

The growth hormone (GH)/insulin-like growth factor I (IGF-I) axis is involved in metabolic control. Malnutrition reduces IGF-I and modifies the thermogenic capacity of brown adipose tissue (BAT). Leptin has effects on the GH/IGF-I axis and the function of BAT, but its interaction with IGF-I and the mechanisms involved in the regulation of thermogenesis remains unknown. We studied the GH/IGF-I axis and activation of IGF-I-related signaling and metabolism related to BAT thermogenesis in chronic central leptin infused (L), pair-fed (PF), and control rats. Hypothalamic somatostatin mRNA levels were increased in PF and decreased in L, while pituitary GH mRNA was reduced in PF. Serum GH and IGF-I concentrations were decreased only in PF. In BAT, the association between suppressor of cytokine signaling 3 and the IGF-I receptor was reduced, and phosphorylation of the IGF-I receptor increased in the L group. Phosphorylation of Akt and cyclic AMP response element binding protein and glucose transporter 4 mRNA levels were increased in L and mRNA levels of uncoupling protein-1 (UCP-1) and enzymes involved in lipid anabolism reduced in PF. These results suggest that modifications in UCP-1 in BAT and changes in the GH/IGF-I axis induced by negative energy balance are dependent upon leptin levels.

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PSI-1 A systematic review and meta-analysis of GWAS and gene expression results of Holstein cattle under negative energy balance and ketosis

Journal of Animal Science ◽

10.1093/jas/skaa278.478 ◽

2020 ◽

Vol 98 (Supplement_4) ◽

pp. 265-266

Author(s):

Riani Ananda Nunes Soares ◽

Giovana Vargas ◽

Malane M Muniz ◽

Maria Amelia Menck Soares ◽

Angela Canovas ◽

...

Keyword(s):

Gene Expression ◽

Systematic Review ◽

Energy Balance ◽

Gene Network ◽

Meta Analysis ◽

Significant Snps ◽

Negative Energy ◽

Negative Energy Balance ◽

Differentially Expressed ◽

Metabolic Conditions

Abstract Development of ketosis in high-producing dairy cows contributes to animal health issues and highlights the need for better understanding the genetic basis of metabolic diseases. Thus, the aim of this study was to evaluate the pattern of differential gene expression in liver of cows under negative energy balance (NEB), subclinical, and clinical ketosis through a systematic review and meta-analysis of published gene expression and genome-wide association studies (GWAS) results. After screening of the 118 articles found in the systematic review, 20 articles were included in the analysis. For this, 430 significant SNPs identified by GWAS were investigated to see if they were located within genes reported in gene expression studies. A permutation approach was used to identify the biological pathways associated with the metabolic conditions studied. A gene network was created using the differentially expressed genes harboring significant SNPs and a QTL enrichment analysis was performed to identify potential positional candidate loci. This study revealed 14 genes that are differentially expressed in the liver of cows in different metabolic conditions, which harbor 24 significant polymorphisms in reported GWAS. Three significant metabolic pathways were associated with NEB, subclinical and clinical ketosis. In addition, two important genes, PPARA and ACACA, were identified as differentially expressed in the three metabolic conditions. Gene network analysis revealed co-expression interactions among 34 genes associated with functions involving fatty acid transport and metabolism. The genes FN1 and PTK2 were enriched for QTL previously associated with the trait “ketosis” on chromosome 2 and with the trait “milk iron content” on chromosome 14, respectively. These findings improve the understanding of negative energy balance and ketosis in dairy cows, which could enhance selection for cows less susceptible to ketosis and help with the development of potential biomarkers for early diagnosis and prevention of ketosis.

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Energy Balance Indicators during the Transition Period and Early Lactation of Purebred Holstein and Simmental Cows and Their Crosses

Animals ◽

10.3390/ani11020309 ◽

2021 ◽

Vol 11 (2) ◽

pp. 309

Author(s):

Deise Aline Knob ◽

André Thaler Neto ◽

Helen Schweizer ◽

Anna C. Weigand ◽

Roberto Kappes ◽

...

Keyword(s):

Energy Balance ◽

Milk Yield ◽

Milk Composition ◽

Negative Energy ◽

The Other ◽

Negative Energy Balance ◽

Metabolic Energy ◽

Genetic Groups ◽

Significant Difference ◽

Fat Thickness

Crossbreeding in dairy cattle has been used to improve functional traits, milk composition, and efficiency of Holstein herds. The objective of the study was to compare indicators of the metabolic energy balance, nonesterified fatty acids (NEFA), beta-hydroxybutyrate (BHBA), glucose, body condition score (BCS) back fat thickness (BFT), as well as milk yield and milk composition of Holstein and Simmental cows, and their crosses from the prepartum period until the 100th day of lactation at the Livestock Center of the Ludwig Maximilians University (Munich, Germany). In total, 164 cows formed five genetic groups according to their theoretic proportion of Holstein and Simmental genes as follows: Holstein (100% Holstein; n = 9), R1-Hol (51–99% Holstein; n = 30), first generation (F1) crossbreds (50% Holstein, 50% Simmental; n = 17), R1-Sim (1–49% Holstein; n = 81) and Simmental (100% Simmental; n = 27). The study took place between April 2018 and August 2019. BCS, BFT blood parameters, such as BHBA, glucose, and NEFA were recorded weekly. A mixed model analysis with fixed effects breed, week (relative to calving), the interaction of breed and week, parity, calving year, calving season, milking season, and the repeated measure effect of cow was used. BCS increased with the Simmental proportion. All genetic groups lost BCS and BFT after calving. Simmental cows showed lower NEFA values. BHBA and glucose did not differ among genetic groups, but they differed depending on the week relative to calving. Simmental and R1-Sim cows showed a smaller effect than the other genetic groups regarding changes in body weight, BCS, or back fat thickness after a period of a negative energy balance after calving. There was no significant difference for milk yield among genetic groups, although Simmental cows showed a lower milk yield after the third week after calving. Generally, Simmental and R1-Simmental cows seemed to deal better with a negative energy balance after calving than purebred Holstein and the other crossbred lines. Based on a positive heterosis effect of 10.06% for energy corrected milk (ECM), the F1, however, was the most efficient crossbred line.

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Negative energy balance during military training: the role of contextual limitations

Appetite ◽

10.1016/j.appet.2021.105263 ◽

2021 ◽

pp. 105263

Author(s):

Keyne Charlot

Keyword(s):

Energy Balance ◽

Military Training ◽

Negative Energy ◽

Negative Energy Balance

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Metabolic Adaptations to Dynamic Energy Requirements during Lactation and Pregnancy in Dairy Cows with Varying Proportions of Holstein and Simmental Breed

Proceedings ◽

10.3390/ieca2020-08833 ◽

2020 ◽

Vol 73 (1) ◽

pp. 9

Author(s):

Deise Aline Knob ◽

André Thaler Neto ◽

Helen Schweizer ◽

Anna Weigand ◽

Roberto Kappes ◽

...

Keyword(s):

Energy Balance ◽

Dairy Cows ◽

Fixed Effects ◽

Mixed Model ◽

Negative Energy ◽

Negative Energy Balance ◽

Repeated Measure ◽

Holstein Cows ◽

Mixed Model Analysis ◽

Genetic Groups

Depending on the breed or crossbreed line, cows have to cope with a more or less severe negative energy balance during the period of high milk yields in early lactation, which can be detected by beta-hydroxybutyrate (BHBA) and non-esterified fatty acids (NEFAs) in blood. Preventing cows from undergoing a severe negative energy balance by breeding and/or feeding measures is likely to be supported by the public and may help to improve the sustainability of milk production. The aim was to compare BHBA and NEFA concentrations in the blood of Holstein and Simmental cows and their crosses during the prepartum period until the end of lactation. In total, 164 cows formed five genetic groups according to their theoretic proportion of Holstein and Simmental genes as follows: Holstein (100% Holstein; n = 9), R1-Hol (51–99% Holstein; n = 30), F1 crossbreds (50% Holstein, 50% Simmental; n = 17), R1-Sim (1–49% Holstein; n = 81) and Simmental (100% Simmental; n = 27). NEFA and BHBA were evaluated once a week between April 2018 and August 2019. A mixed model analysis with fixed effects breed, week (relative to calving), the interaction of breed and week, parity, calving year, calving season, milking season, and the repeated measure effect on cows was used. Holstein cows had higher NEFAs (0.196 ± 0.013 mmol/L), and Simmental cows had the lowest NEFA concentrations (0.147 ± 0.008 mmol/L, p = 0.03). R1-Sim, F1 and R1-Hol cows had intermediate values (0.166 ± 0.005, 0.165 ± 0.010, 0.162 ± 0.008 mmol/L; respectively). The highest NEFA value was found in the first week after calving (0.49 ± 0.013 mmol/L). BHBA did not differ among genetic groups (p = 0.1007). There was, however, an interaction between the genetic group and week (p = 0.03). While Simmental, R1-Sim and F1 cows had the highest BHBA value, the second week after calving (0.92 ± 0.07 and 1.05 ± 0.04, and 1.10 ± 0.10 mmol/L, respectively), R1-Hol and Holstein cows showed the BHBA peak at the fourth week after calving (1.16 ± 0.07 and 1.36 ± 0.12 mmol/L, respectively). Unexpectedly, Holstein cows had a high BHBA peak again at week 34 after calving (1.68 ± 0.21 mmol/L). The genetic composition of the cows affects NEFA and BHBA. Simmental and R1-Sim cows mobilize fewer body reserves after calving. Therefore, dairy cows with higher degrees of Simmental origin might be more sustainable in comparison with Holstein genetics in the present study.

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The Capacity of Holstein-Friesian and Simmental Cows to Correct a Negative Energy Balance in Relation to Their Performance Parameters, Course of Lactation, and Selected Milk Components

Animals ◽

10.3390/ani11061674 ◽

2021 ◽

Vol 11 (6) ◽

pp. 1674

Author(s):

Ilona Strączek ◽

Krzysztof Młynek ◽

Agata Danielewicz

Keyword(s):

Fatty Acid ◽

Energy Balance ◽

Dairy Cows ◽

Body Condition ◽

Body Condition Score ◽

Negative Energy ◽

Negative Energy Balance ◽

Holstein Friesian ◽

Condition Score ◽

Peak Lactation

A significant factor in improving the performance of dairy cows is their physiological ability to correct a negative energy balance (NEB). This study, using Simmental (SIM) and Holstein-Friesian (HF) cows, aimed to assess changes in NEB (non-esterified fatty acid; body condition score; and C16:0, C18:0, and C18:1) and its effect on the metabolic efficiency of the liver (β-hydroxybutyrate and urea). The effects of NEB on daily yield, production at peak lactation and its duration, and changes in selected milk components were assessed during complete lactation. Up to peak lactation, the loss of the body condition score was similar in both breeds. Subsequently, SIM cows more efficiently restored their BCS. HF cows reached peak lactation faster and with a higher milk yield, but they were less able to correct NEB. During lactation, their non-esterified fatty acid, β-hydroxybutyrate, C16:0, C18:0, C18:1, and urea levels were persistently higher, which may indicate less efficient liver function during NEB. The dynamics of NEB were linked to levels of leptin, which has anorectic effects. Its content was usually higher in HF cows and during intensive lactogenesis. An effective response to NEB may be exploited to improve the production and nutritional properties of milk. In the long term, it may extend dairy cows’ productive life and increase lifetime yield.

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Energy Balance and Energy Availability During a Selection Course for Belgian Paratroopers

Military Medicine ◽

10.1093/milmed/usab140 ◽

2021 ◽

Author(s):

Patrick Mullie ◽

Pieter Maes ◽

Laurens van Veelen ◽

Damien Van Tiggelen ◽

Peter Clarys

Keyword(s):

Physical Activity ◽

Energy Balance ◽

Energy Expenditure ◽

Metabolic Rate ◽

Energy Intake ◽

Rest Metabolic Rate ◽

Negative Energy ◽

Fat Free Mass ◽

Negative Energy Balance ◽

Energy Availability

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.

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