A Negative Energy Balance Is Associated with Metabolic Dysfunctions in the Hypothalamus of a Humanized Preclinical Model of Alzheimer’s Disease, the 5XFAD Mouse

Increasing evidence links metabolic disorders with neurodegenerative processes including Alzheimer’s disease (AD). Late AD is associated with amyloid (Aβ) plaque accumulation, neuroinflammation, and central insulin resistance. Here, a humanized AD model, the 5xFAD mouse model, was used to further explore food intake, energy expenditure, neuroinflammation, and neuroendocrine signaling in the hypothalamus. Experiments were performed on 6-month-old male and female full transgenic (Tg5xFAD/5xFAD), heterozygous (Tg5xFAD/-), and non-transgenic (Non-Tg) littermates. Although histological analysis showed absence of Aβ plaques in the hypothalamus of 5xFAD mice, this brain region displayed increased protein levels of GFAP and IBA1 in both Tg5xFAD/- and Tg5xFAD/5xFAD mice and increased expression of IL-1β in Tg5xFAD/5xFAD mice, suggesting neuroinflammation. This condition was accompanied by decreased body weight, food intake, and energy expenditure in both Tg5xFAD/- and Tg5xFAD/5xFAD mice. Negative energy balance was associated with altered circulating levels of insulin, GLP-1, GIP, ghrelin, and resistin; decreased insulin and leptin hypothalamic signaling; dysregulation in main metabolic sensors (phosphorylated IRS1, STAT5, AMPK, mTOR, ERK2); and neuropeptides controlling energy balance (NPY, AgRP, orexin, MCH). These results suggest that glial activation and metabolic dysfunctions in the hypothalamus of a mouse model of AD likely result in negative energy balance, which may contribute to AD pathogenesis development.

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Adolescent Inhalant Abuse Results in Adrenal Dysfunction and a Hypermetabolic Phenotype with Persistent Growth Impairments

Neuroendocrinology ◽

10.1159/000493686 ◽

2018 ◽

Vol 107 (4) ◽

pp. 340-354 ◽

Cited By ~ 3

Author(s):

Rose Crossin ◽

Zane B. Andrews ◽

Natalie A. Sims ◽

Terence Pang ◽

Michael Mathai ◽

...

Keyword(s):

Energy Balance ◽

Food Intake ◽

Energy Expenditure ◽

Adrenal Insufficiency ◽

Fasting Blood Glucose ◽

Negative Energy ◽

Negative Energy Balance ◽

Metabolic Phenotype ◽

Adolescent Male ◽

Inhalant Abuse

Background/Aims: Abuse of toluene products (e.g., glue-sniffing) primarily occurs during adolescence and has been associated with appetite suppression and weight impairments. However, the metabolic phenotype arising from adolescent inhalant abuse has never been fully characterised, and its persistence during abstinence and underlying mechanisms remain unknown. Methods: Adolescent male Wistar rats (post-natal day 27) were exposed to inhaled toluene (10,000 ppm) (n = 32) or air (n = 48) for 1 h/day, 3 days/week for 4 weeks, followed by 4 weeks of abstinence. Twenty air rats were pair-fed to the toluene group, to differentiate the direct effects of toluene from under-nutrition. Food intake, weight, and growth were monitored. Metabolic hormones were measured after exposure and abstinence periods. Energy expenditure was measured using indirect calorimetry. Adrenal function was assessed using adrenal histology and hormone testing. Results: Inhalant abuse suppressed appetite and increased energy expenditure. Reduced weight gain and growth were observed in both the toluene and pair-fed groups. Compared to the pair-fed group, and despite normalisation of food intake, the suppression of weight and growth for toluene-exposed rats persisted during abstinence. After exposure, toluene-exposed rats had low fasting blood glucose and insulin compared to the air and pair-fed groups. Consistent with adrenal insufficiency, adrenal hypertrophy and increased basal adrenocorticotropic hormone were observed in the toluene-exposed rats, despite normal basal corticosterone levels. Conclusions: Inhalant abuse results in negative energy balance, persistent growth impairment, and endocrine changes suggestive of adrenal insufficiency. We conclude that adrenal insufficiency contributes to the negative energy balance phenotype, potentially presenting a significant additional health risk for inhalant users.

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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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Prolonged Volatile Anesthetic Exposure Exacerbates Cognitive Impairment and Neuropathology in the 5xFAD Mouse Model of Alzheimer’s Disease

Journal of Alzheimer s Disease ◽

10.3233/jad-210374 ◽

2021 ◽

pp. 1-12

Author(s):

Fanglei Han ◽

Jia Zhao ◽

Guoqing Zhao

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Mouse Model ◽

Volatile Anesthetics ◽

Model Of Alzheimer’S Disease ◽

Short Term Exposure ◽

5Xfad Mouse ◽

Anesthetic Exposure ◽

5Xfad Mice

Background: Alzheimer’s disease (AD) is a progressive neurodegenerative disease which shows a set of symptoms involving cognitive changes and psychological changes. Given that AD is the most common form of dementia in aging population and the increasing demand for anesthesia/surgery with aging, there has been significant interest in the exact impact of volatile anesthetics on cognitive function and pathological alterations in AD population. Objective: This study aimed to investigate behavioral changes and neuropathology in the 5xFAD mouse model of Alzheimer’s disease with short-term exposure or long-term exposure to desflurane, sevoflurane, or isoflurane. Methods: In this study, we exposed 5xFAD mouse model of AD to isoflurane, sevoflurane, or desflurane in two different time periods (30 min and 6 h), and the memory related behaviors as well as the pathological changes in 5xFAD mice were evaluated 7 days after the anesthetic exposure. Results: We found that short-term exposure to volatile anesthetics did not affect hippocampus dependent memory and the amyloid-β (Aβ) deposition in the brain. However, long-term exposure to sevoflurane or isoflurane significantly increased the Aβ deposition in CA1 and CA3 regions of hippocampus, as well as the glial cell activation in amygdala. Besides, the PSD-95 expression was decreased in 5xFAD mice with exposure to sevoflurane or isoflurane and the caspase-3 activation was enhanced in isoflurane, sevoflurane, and desflurane groups. Conclusion: Our results demonstrate the time-dependent effects of common volatile anesthetics and implicate that desflurane has the potential benefits to prolonged anesthetic exposure in AD patients.

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Session 2: Calorie-Cutting Keys

Effective Weight Loss ◽

10.1093/med:psych/9780190232009.003.0002 ◽

2016 ◽

pp. 15-26

Author(s):

Evan M. Forman ◽

Meghan L. Butryn

Keyword(s):

Energy Balance ◽

Food Intake ◽

Eating Behavior ◽

Negative Energy ◽

Negative Energy Balance ◽

Calorie Intake ◽

Self Monitoring ◽

Serving Size ◽

High Calorie

This chapter (Session 2) discusses the importance of self-monitoring to gain awareness of calorie intake and to recognize patterns in eating behavior. Clients are provided with information on how to self-monitor food intake, including recording type of food, serving size, method of preparation, and time of eating. Strategies for beginning to reduce calories are discussed, such as limiting high-calorie foods in the environment, eating regular meals, and planning meals in advance. The idea of achieving a negative energy balance is introduced, meaning that in order to lose weight, clients must expend a greater amount of energy than they consume in the form of calories.

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Disturbance of the reproductive axis induced by negative energy balance

Reproduction Fertility and Development ◽

10.1071/r98024 ◽

1998 ◽

Vol 10 (1) ◽

pp. 65 ◽

Cited By ~ 20

Author(s):

Stephen J. Judd

Keyword(s):

Energy Balance ◽

Energy Expenditure ◽

Tertiary Structure ◽

Interleukin 2 ◽

Growth Hormone Secretion ◽

Negative Energy ◽

Negative Energy Balance ◽

Thyrotrophin Releasing Hormone ◽

Releasing Hormone ◽

Crf Neurons

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.

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Metabolic adaptations during negative energy balance and their potential impact on appetite and food intake

Proceedings of The Nutrition Society ◽

10.1017/s0029665118002811 ◽

2019 ◽

Vol 78 (3) ◽

pp. 279-289 ◽

Cited By ~ 4

Author(s):

Nuno Casanova ◽

Kristine Beaulieu ◽

Graham Finlayson ◽

Mark Hopkins

Keyword(s):

Weight Loss ◽

Energy Balance ◽

Food Intake ◽

Negative Energy ◽

Fat Free Mass ◽

Negative Energy Balance ◽

Energy Deficit ◽

Behavioural Responses ◽

Compensatory Responses ◽

Metabolic Adaptations

This review examines the metabolic adaptations that occur in response to negative energy balance and their potential putative or functional impact on appetite and food intake. Sustained negative energy balance will result in weight loss, with body composition changes similar for different dietary interventions if total energy and protein intake are equated. During periods of underfeeding, compensatory metabolic and behavioural responses occur that attenuate the prescribed energy deficit. While losses of metabolically active tissue during energy deficit result in reduced energy expenditure, an additional down-regulation in expenditure has been noted that cannot be explained by changes in body tissue (e.g. adaptive thermogenesis). Sustained negative energy balance is also associated with an increase in orexigenic drive and changes in appetite-related peptides during weight loss that may act as cues for increased hunger and food intake. It has also been suggested that losses of fat-free mass (FFM) could also act as an orexigenic signal during weight loss, but more data are needed to support these findings and the signalling pathways linking FFM and energy intake remain unclear. Taken together, these metabolic and behavioural responses to weight loss point to a highly complex and dynamic energy balance system in which perturbations to individual components can cause co-ordinated and inter-related compensatory responses elsewhere. The strength of these compensatory responses is individually subtle, and early identification of this variability may help identify individuals that respond well or poorly to an intervention.

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ENERGY BALANCE AND VITAL SIGNS IN PEDIATRIC PATIENTS

Orthopaedic Journal of Sports Medicine ◽

10.1177/2325967120s00206 ◽

2020 ◽

Vol 8 (4_suppl3) ◽

pp. 2325967120S0020

Author(s):

Julie A. Young ◽

Jessica Napolitano ◽

Mitchell J. Rauh ◽

Jeanne Nichols ◽

Anastasia N. Fischer

Keyword(s):

Blood Pressure ◽

Heart Rate ◽

Energy Balance ◽

Energy Expenditure ◽

Vital Signs ◽

Negative Energy ◽

Negative Energy Balance ◽

Energy Deficit ◽

Energy Deficiency ◽

Males And Females

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.

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Regulation of serum leptin and its role in the hyperphagia of lactation in the rat

Journal of Endocrinology ◽

10.1677/joe.0.1760193 ◽

2003 ◽

Vol 176 (2) ◽

pp. 193-203 ◽

Cited By ~ 35

Author(s):

RG Denis ◽

G Williams ◽

RG Vernon

Keyword(s):

Energy Balance ◽

Food Intake ◽

Milk Production ◽

Litter Size ◽

High Energy ◽

Negative Energy ◽

Negative Energy Balance ◽

Calorie Intake ◽

Serum Leptin ◽

Nocturnal Rise

The factors regulating serum leptin concentration and its relationship to the hyperphagia of lactation have been investigated in rats. Lactation results in hypoleptinaemia and loss, or at least marked attenuation, of the nocturnal rise in serum leptin. Litter removal resulted in a fall in food intake and restoration of the nocturnal rise in serum leptin. Returning the litter to the mother after a 48-h absence increased food intake and began to reinitiate milk production, but the nocturnal serum leptin levels were still increased at 48 h after litter restoration. Adjusting litter size to four, eight, ten or fourteen pups at parturition resulted in different rates of litter growth and food intake during the subsequent lactation, but had no effect on the degree of hypoleptinaemia. Reducing litter size from ten to four pups at mid-lactation resulted in a transient increase in both serum leptin and pup growth rate, while food intake fell to a level found in rats suckling four pups throughout lactation. Reducing milk production by injection of bromocriptine increased serum leptin, but did not restore the nocturnal rise in serum leptin; food intake decreased, but remained much higher than in non-lactating rats. Feeding a varied, high-energy diet resulted in a decrease in the weight of food ingested, but no change in calorie intake, and had no effect on the hypoleptinaemia. These studies suggested that the hypoleptinaemia of lactating rats is due to negative energy balance, but the loss of the nocturnal rise in serum leptin is due to the suckling stimulus. The negative energy balance of lactation does not appear to be caused by a physical constraint on food intake. While the hypoleptinaemia should facilitate the hyperphagia of lactation, other orexigenic signals must also be involved.

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Relationships between energy balance and health traits of dairy cattle in early lactation

BSAP Occasional Publication ◽

10.1017/s146398150004320x ◽

1999 ◽

Vol 24 ◽

pp. 171-175 ◽

Cited By ~ 1

Author(s):

B. L. Collard ◽

P. J. Boettcher ◽

J. C. M. Dekkers ◽

L. R. Schaeffer ◽

D. Petitclerc

Keyword(s):

Energy Balance ◽

Food Intake ◽

Total Energy ◽

Milk Production ◽

Additive Genetic Variance ◽

Negative Energy ◽

Negative Energy Balance ◽

Energy Deficit ◽

Research Station ◽

Daily Energy

AbstractData were records of daily food intake and milk production, periodic measures of milk composition and all health and reproductive information from 140 multiparous Holstein cows involved in various experiments at the Agriculture Canada dairy research station in Lennoxville, Quebec. Energy concentrations of the total mixed rations were also available. Daily energy balance was calculated by multiplying the food intake by the concentration of energy in the diet and then subtracting from this quantity the expected (National Research Council) amount of energy required for maintenance (based on parity and body weight) and for milk production (based on yield and concentrations of fat, protein and lactose). Four energy balance traits were defined: (1) average daily energy balance within the first 10 to 100 days of lactation, (2) minimum daily energy balance, (3) days in negative energy balance and (4) total energy deficit during the period of negative energy balance. Health traits were the numbers of incidences of each of the following: (1) all udder problems, (2) mastitis, (3) all locomotive problems, (4) laminitis, (5) digestive problems and (6) reproductive problems. Reproductive traits were the number of days to first observed oestrous and number of inseminations. Phenotypic relationships between energy balance and health were investigated by regressing the energy balance traits on each health trait. Parity and treatment (according to the research trial that the cow was involved with) were also included in the model. Genetic parameters were estimated with restricted maximum likelihood and a model that included effects of parity, treatment and animal. Phenotypically, several significant (P<0.10) relationships between energy balance and health were observed. Cows with longer periods of negative energy balance had increased digestive problems. Cows with greater total energy deficit had more digestive problems and laminitis. Estimates of heritabilities for energy intake and milk energy were 0.42 and 0.12, respectively but estimates of heritability for all energy balance traits were zero. The low estimates for these traits may have been due to (1) low true additive genetic variance, (2) small amount of data, or (3) relatively few genetic ties among cows.

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