Brs3 neurons in the mouse dorsomedial hypothalamus regulate body temperature, energy expenditure, and heart rate, but not food intake

Six adult white-tailed deer (Odocoileus virginianus borealis) were exposed to 165 periods of 12 consecutive hours of controlled constant ambient temperature in an indirect respiration calorimeter. Temperatures among periods varied from 38 to 0 (summer) or to −20C (fall, winter, spring). Traits measured were energy expenditure (metabolic rate), proportion of time spent standing, heart rate, and body temperature, the latter two using telemetry. The deer used body posture extensively as a means of maintaining body energy equilibrium. Energy expenditure was increased at low ambient temperature to combat cold and to maintain relatively constant body temperature. Changes in heart rate paralleled changes in energy expenditure. In a limited number of comparisons, slight wind chill was combatted through behavioral means with no effect on energy expenditure. The reaction of deer to varying ambient temperatures was not the same in all seasons of the year.

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Gqα/G11α deficiency in dorsomedial hypothalamus leads to obesity resulting from decreased energy expenditure and impaired sympathetic nerve activity

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00059.2020 ◽

2020 ◽

Author(s):

Eric A. Wilson ◽

Hui Sun ◽

Zhenzhong Cui ◽

Marshal T. Jahnke ◽

Mritunjay Pandey ◽

...

Keyword(s):

Gene Expression ◽

Adipose Tissue ◽

Food Intake ◽

Energy Expenditure ◽

Energy Homeostasis ◽

Dorsomedial Hypothalamus ◽

Ambient Temperatures ◽

Brown Adipose ◽

Inhibit Food Intake ◽

Specific Deletion

The G protein subunits Gqα and G11α (Gq/11α) couple receptors to phospholipase C, leading to increased intracellular calcium. In this study we investigated the consequences of Gq/11α deficiency in the dorsomedial hypothalamus (DMH), a critical site for the control of energy homeostasis. Mice with DMH-specific deletion of Gq/11α (DMHGq/11KO) were generated by stereotaxic injection of AAV-Cre-GFP into the DMH of Gqαflox/flox:G11α-/- mice. Compared to control mice that received DMH injection of AAV-GFP, DMHGq/11KO mice developed obesity associated with reduced energy expenditure without significant changes in food intake or physical activity. DMHGq/11KO mice showed no defects in the ability of the melanocortin agonist melanotan II to acutely stimulate energy expenditure or to inhibit food intake. At room temperature (22oC) DMHGq/11KO mice showed reduced sympathetic nervous system activity in brown adipose tissue (BAT) and heart, accompanied with decreased basal BAT Ucp1 gene expression and lower heart rates. These mice were cold intolerant when acutely exposed to cold (6oC for 5 hours) and had decreased cold-stimulated BAT Ucp1 gene expression. DMHGq/11KO mice also failed to adapt to gradually declining ambient temperatures and to develop adipocyte browning in inguinal white adipose tissue although their BAT Ucp1 was proportionally stimulated. Consistent with impaired cold-induced thermogenesis, the onset of obesity in DMHGq/11KO mice was significantly delayed when housed under thermoneutral conditions (30ºC). Thus, our results show that Gqα and G11α in the DMH are required for the control of energy homeostasis by stimulating energy expenditure and thermoregulation.

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Discrete TrkB-expressing neurons of the dorsomedial hypothalamus regulate feeding and thermogenesis

10.1101/2020.09.02.279745 ◽

2020 ◽

Author(s):

Jessica Houtz ◽

Guey-Ying Liao ◽

Baoji Xu

Keyword(s):

Food Intake ◽

Energy Expenditure ◽

Neuronal Activity ◽

Energy Homeostasis ◽

Preoptic Area ◽

Neurotrophin Receptor ◽

Dorsomedial Hypothalamus ◽

Adaptive Thermogenesis ◽

Regulate Food Intake ◽

Raphe Pallidus

AbstractMutations in the TrkB neurotrophin receptor lead to profound obesity in humans, and expression of TrkB in the dorsomedial hypothalamus (DMH) is critical for maintaining energy homeostasis. However, the functional implications of TrkB-expressing neurons in the DMH (DMHTrkB) on energy expenditure are unclear. Additionally, the neurocircuitry underlying the effect of DMHTrkB neurons on energy homeostasis has not been explored. In this study, we show that activation of DMHTrkB neurons leads to a robust increase in adaptive thermogenesis and energy expenditure without altering heart rate or blood pressure, while silencing DMHTrkB neurons impairs thermogenesis. Furthermore, we reveal neuroanatomically and functionally distinct populations of DMHTrkB neurons that regulate food intake or thermogenesis. Activation of DMHTrkB neurons projecting to the raphe pallidus stimulates thermogenesis and increased energy expenditure, whereas DMHTrkB neurons that send collaterals to the paraventricular hypothalamus and preoptic area inhibit feeding. Together, our findings provide evidence that DMHTrkB neuronal activity plays an important role in regulating energy expenditure and delineate distinct neurocircuits that underly the separate effects of DMHTrkB neuronal activity on food intake and thermogenesis.Brief summaryThis study shows that TrkB-expressing DMH neurons stimulate thermogenesis through projection to raphe pallidus, while inhibiting feeding through collaterals to paraventricular hypothalamus and preoptic area.

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The Effect of Kappa Opioid Receptor Antagonism on Energy Expenditure in the Obese Zucker Rat

Biological Research For Nursing ◽

10.1177/1099800406298774 ◽

2007 ◽

Vol 8 (4) ◽

pp. 294-299 ◽

Cited By ~ 9

Author(s):

Patricia A. Jarosz

Keyword(s):

Body Weight ◽

Food Intake ◽

Body Temperature ◽

Energy Expenditure ◽

Opioid Receptor ◽

Kappa Opioid Receptor ◽

Endogenous Opioids ◽

Zucker Rats ◽

General Activity ◽

Kappa Opioid

Food intake and, subsequently, body weight are influenced by endogenous opioids acting in the central nervous system. Agonists for the opioid receptor increase food intake, whereas antagonists reduce food intake. Body weight, however, is the result of food consumed and energy expended. Although much has been reported about the effect of opioid antagonism on food intake, less has been reported about its effect on energy expended. This study investigated the effect of selective antagonism of the kappa opioid receptor on food intake, body weight, and indicators of energy expenditure in male obese Zucker rats (n= 10). Energy expenditure was measured by indirect calorimetry, whereas general activity and body temperature were measured by implanted radio frequency telemetry. Central administration of 30 µg of the kappa opioid receptor (KOR) antagonist norbinaltorphamine resulted in a significant 34% reduction in food intake (p = .001), a small reduction in body weight, a reduction in resting energy expenditure (p = .06), a reduction in respiratory quotient (p = .06), a 14% reduction in general activity, and a reduction in core body temperature. Reduction in body weight as a result of KOR inhibition in this study was related to a decrease in food intake but not related to an increase in energy expended or activity.

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Defending body mass during food restriction in Acomys russatus: a desert rodent that does not store food

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00156.2005 ◽

2006 ◽

Vol 290 (4) ◽

pp. R881-R891 ◽

Cited By ~ 27

Author(s):

Roee Gutman ◽

Itzhak Choshniak ◽

Noga Kronfeld-Schor

Keyword(s):

Heart Rate ◽

Oxygen Consumption ◽

Body Temperature ◽

Energy Expenditure ◽

Body Mass ◽

Food Restriction ◽

Daily Torpor ◽

Spiny Mice ◽

Desert Rodent ◽

Initial Decrease

Golden spiny mice, which inhabit rocky deserts and do not store food, must therefore employ physiological means to cope with periods of food shortage. Here we studied the physiological means used by golden spiny mice for conserving energy during food restriction and refeeding and the mechanism by which food consumption may influence thermoregulatory mechanisms and metabolic rate. As comparison, we studied the response to food restriction of another rocky desert rodent, Wagner’s gerbil, which accumulates large seed caches. Ten out of 12 food-restricted spiny mice (resistant) were able to defend their body mass after an initial decrease, as opposed to Wagner’s gerbils ( n = 6). Two of the spiny mice (nonresistant) kept losing weight, and their food restriction was halted. In four resistant and two nonresistant spiny mice, we measured heart rate, body temperature, and oxygen consumption during food restriction. The resistant spiny mice significantly ( P < 0.05) reduced energy expenditure and entered daily torpor. The nonresistant spiny mice did not reduce their energy expenditure. The gerbils’ response to food restriction was similar to that of the nonresistant spiny mice. Resistant spiny mice leptin levels dropped significantly ( n = 6, P < 0.05) after 24 h of food restriction, and continued to decrease throughout food restriction, as did body fat. During refeeding, although the golden spiny mice gained fat, leptin levels were not correlated with body mass ( r2 = 0.014). It is possible that this low correlation allows them to continue eating and accumulate fat when food is plentiful.

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Leptin receptor neurons in the dorsomedial hypothalamus are key regulators of energy expenditure and body weight, but not food intake

Molecular Metabolism ◽

10.1016/j.molmet.2014.07.008 ◽

2014 ◽

Vol 3 (7) ◽

pp. 681-693 ◽

Cited By ~ 91

Author(s):

Kavon Rezai-Zadeh ◽

Sanghou Yu ◽

Yanyan Jiang ◽

Amanda Laque ◽

Candice Schwartzenburg ◽

...

Keyword(s):

Body Weight ◽

Food Intake ◽

Energy Expenditure ◽

Leptin Receptor ◽

Dorsomedial Hypothalamus ◽

Receptor Neurons

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Dorsomedial hypothalamus mediates autonomic, neuroendocrine, and locomotor responses evoked from the medial preoptic area

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00574.2009 ◽

2010 ◽

Vol 298 (1) ◽

pp. R130-R140 ◽

Cited By ~ 19

Author(s):

Joseph L. Hunt ◽

Dmitry V. Zaretsky ◽

Sumit Sarkar ◽

Joseph A. DiMicco

Keyword(s):

Heart Rate ◽

Body Temperature ◽

Preoptic Area ◽

Medial Preoptic Area ◽

Behavioral Changes ◽

Baseline Heart Rate ◽

Plasma Acth ◽

Temperature Plasma ◽

Dorsomedial Hypothalamus ◽

Inhibitory Tone

Previous studies suggest that sympathetic responses evoked from the preoptic area in anesthetized rats require activation of neurons in the dorsomedial hypothalamus. Disinhibition of neurons in the dorsomedial hypothalamus in conscious rats produces physiological and behavioral changes resembling those evoked by microinjection of muscimol, a GABAA receptor agonist and neuronal inhibitor, into the medial preoptic area. We tested the hypothesis that all of these effects evoked from the medial preoptic area are mediated through neurons in the dorsomedial hypothalamus by assessing the effect of bilateral microinjection of muscimol into the DMH on these changes. After injection of vehicle into the dorsomedial hypothalamus, injection of muscimol into the medial preoptic area elicited marked increases in heart rate, arterial pressure, body temperature, plasma ACTH, and locomotor activity and also increased c-Fos expression in the hypothalamic paraventricular nucleus, a region known to control the release of ACTH from the adenohypophysis. Prior bilateral microinjection of muscimol into the dorsomedial hypothalamus produced a modest depression of baseline heart rate and body temperature but completely abolished all changes evoked from the medial preoptic area. Microinjection of muscimol just anterior to the dorsomedial hypothalamus had no effect on autonomic and neuroendocrine changes evoked from the medial preoptic area. Thus, activity of neurons in the dorsomedial hypothalamus mediates a diverse array of physiological and behavioral responses elicited from the medial preoptic area, suggesting that the latter region represents an important source of inhibitory tone to key neurons in the dorsomedial hypothalamus.

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Mice lacking melanin-concentrating hormone receptor 1 demonstrate increased heart rate associated with altered autonomic activity

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00134.2004 ◽

2004 ◽

Vol 287 (4) ◽

pp. R749-R758 ◽

Cited By ~ 64

Author(s):

Annika Åstrand ◽

Mohammad Bohlooly-Y ◽

Sara Larsdotter ◽

Margit Mahlapuu ◽

Harriet Andersén ◽

...

Keyword(s):

Heart Rate ◽

Nervous System ◽

Autonomic Nervous System ◽

Body Temperature ◽

Energy Expenditure ◽

Dark Phase ◽

Wild Type ◽

Autonomic Nervous ◽

Significant Difference ◽

Melanin Concentrating Hormone

Melanin-concentrating hormone (MCH) plays an important role in energy balance. The current studies were carried out on a new line of mice lacking the rodent MCH receptor (MCHR1−/− mice). These mice confirmed the previously reported lean phenotype characterized by increased energy expenditure and modestly increased caloric intake. Because MCH is expressed in the lateral hypothalamic area, which also has an important role in the regulation of the autonomic nervous system, heart rate and blood pressure were measured by a telemetric method to investigate whether the increased energy expenditure in these mice might be due to altered autonomic nervous system activity. Male MCHR1−/− mice demonstrated a significantly increased heart rate [24-h period: wild type 495 ± 4 vs. MCHR1−/− 561 ± 8 beats/min ( P < 0.001); dark phase: wild type 506 ± 8 vs. MCHR1−/− 582 ± 9 beats/min ( P < 0.001); light phase: wild type 484 ± 13 vs. MCHR1−/− 539 ± 9 beats/min ( P < 0.005)] with no significant difference in mean arterial pressure [wild type 110 ± 0.3 vs. MCHR1−/− 113 ± 0.4 mmHg ( P > 0.05)]. Locomotor activity and core body temperature were higher in the MCHR1−/− mice during the dark phase only and thus temporally dissociated from heart rate differences. On fasting, wild-type animals rapidly downregulated body temperature and heart rate. MCHR1−/− mice displayed a distinct delay in the onset of this downregulation. To investigate the mechanism underlying these differences, autonomic blockade experiments were carried out. Administration of the adrenergic antagonist metoprolol completely reversed the tachycardia seen in MCHR1−/− mice, suggesting an increased sympathetic tone.

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The Epidermal Barrier is Indispensable for Systemic Energy Homeostasis

10.1101/2020.09.01.277723 ◽

2020 ◽

Author(s):

Vibeke Kruse ◽

Ditte Neess ◽

Ann-Britt Marcher ◽

Mie Rye Wæde ◽

Julie Vistisen ◽

...

Keyword(s):

Food Intake ◽

Body Temperature ◽

Energy Expenditure ◽

Barrier Function ◽

Physiological Responses ◽

Metabolic Phenotype ◽

Oral Glucose ◽

Skin Lipid ◽

Epidermal Barrier ◽

Diet Induced Obesity

ABSTRACTObjectivesHomeostatic regulation of body temperature is fundamental to mammalian physiology and is controlled by acute and chronic responses of local, endocrine and neuronal regulators. Although the skin is the largest sensory organ of the human body, and plays a fundamental role in regulating body temperature, it is surprising that adaptive alterations in skin functions and morphology only vaguely have been associated with physiological responses to cold stress or sensation of ambient temperatures.MethodsTo unravel the physiological responses to a compromised epidermal barrier in detail we have used animal models with either defects in skin lipid metabolism (ACBP-/- and skin-specific ACBP-/- knockout mice) or defects in skin structural proteins (ma/ma Flgft/ft). The primary objective was to clarify how defects in epidermal barrier function affect 1) energy expenditure by indirect calorimetry, 2) response to high fat feeding and a high oral glucose load and 3) expression of brown-selective gene programs by quantitative PCR in inguinal WAT (iWAT).ResultsWe show that mice with a compromised epidermal barrier function exhibit increased energy expenditure, increased food intake, browning of the iWAT, and resistance to diet-induced obesity. The metabolic phenotype, including browning of the iWAT, is reversed by housing the mice at thermoneutrality (30°C) or by pharmacological β-adrenergic blocking. These findings show that a compromised epidermal barrier induces a β-adrenergic response that increases energy expenditure and browning of the white adipose tissue to maintain a normal body temperature.ConclusionOur findings show that the epidermal barrier plays a key role in maintaining systemic metabolic homeostasis.HighlightsEnergy expenditure is significantly augmented in mice with impaired epidermal barrier.Mice with compromised barrier display increased food intake while maintaining normal bodyweight.Mice with an impaired epidermal barrier are resistant to diet-induced obesity and insulin resistance.Compromised barrier function induces expression of brown-selective gene programs in iWAT.Thermoneutral housing or blocking β-adrenergic signaling prevents induction of brite-selective genes in iWAT and reverses food intake.

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Preoptic BRS3 neurons increase body temperature and heart rate via multiple pathways

10.1101/2021.03.04.433948 ◽

2021 ◽

Author(s):

Ramón A Pi&ntildeol ◽

Allison S Mogul ◽

Colleen K Hadley ◽

Atreyi Saha ◽

Chia Li ◽

...

Keyword(s):

Heart Rate ◽

Body Temperature ◽

Neural Circuits ◽

Preoptic Area ◽

Behavioral Responses ◽

Orphan Receptor ◽

Dorsomedial Hypothalamus ◽

Neuronal Populations ◽

Fine Tune

The preoptic area (POA) is a key region controlling body temperature (Tb), dictating thermogenic, cardiovascular, and behavioral responses to regulate Tb. Known POA neuronal populations reduce Tb when activated; a population that increases Tb upon activation has not yet been reported. We now identify bombesin-like receptor 3 (BRS3)-expressing POA (POABRS3) neurons as having this missing functionality. BRS3 is an orphan receptor that regulates energy and cardiovascular homeostasis, but the relevant neural circuits are incompletely understood. In mice, we demonstrate that POABRS3 neuronal activation increases Tb, heart rate, and blood pressure sympathetically, via projections to the paraventricular nucleus of the hypothalamus and dorsomedial hypothalamus. Acute POABRS3 inhibition reduces Tb. Long-term inactivation of POABRS3 neurons increased Tb variability with exaggerated Tb changes, overshooting both increases and decreases in Tb set point. BRS3 marks preoptic populations that regulate Tb and heart rate, contribute to cold-defense and fine-tune feedback control of Tb. These findings advance understanding of homeothermy, a defining feature of mammalian biology.

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