An assessment of thermoneutral housing conditions on murine cardiometabolic function

2021 ◽  
Author(s):  
Xian Chen ◽  
Eliza Bollinger ◽  
Teresa Cunio ◽  
Federico Damilano ◽  
John C. Stansfield ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Mouse Models ◽  
Room Temperature ◽  
Systolic Function ◽  
Housing Conditions ◽  
High Fat ◽  
Adaptive Thermogenesis ◽  
Brown Adipose ◽  
Cardiometabolic Function

Mouse models are used to model human diseases and perform pharmacological efficacy testing to advance therapies to humans; most of these studies are conducted in room temperature conditions. At room temperature (22°C), mice are cold stressed and must utilize brown adipose tissue (BAT) to maintain body temperature. This cold stress increases catecholamine tone to maintain adipocyte lipid release via lipolysis, which will fuel adaptive thermogenesis. Maintaining rodents at thermoneutral temperatures (28°C) ameliorates the need for adaptive thermogenesis, thus reducing catecholamine tone and BAT activity. Cardiovascular tone is also determined by catecholamine levels in rodents, as beta adrenergic stimuli are primary drivers of not only lipolytic, but also ionotropic and chronotropic responses. As mice have increased catecholamine tone at room temperature, we investigated how thermoneutral housing conditions would impact cardiometabolic function. Here, we show a rapid and reversible effect of thermoneutrality on both heart rate and blood pressure in chow fed animals, which was blunted in animals fed high fat diet. Animals subjected to transverse aortic constriction displayed compensated hypertrophy at room temperature, while animals displayed less hypertrophy and trends towards worse systolic function at thermoneutrality. Despite these dramatic changes in blood pressure and heart rate at thermoneutral housing conditions, enalapril effectively improved cardiac hypertrophy and gene expression alterations. There were surprisingly few differences in cardiac parameters in high fat fed animals at thermoneutrality. Overall, these data suggest that thermoneutral housing may alter some aspects of cardiac remodeling in preclinical mouse models of heart failure.

scholarly journals Inactivation of the adrenergic receptor β2 disrupts glucose homeostasis in mice

2014 ◽  
Vol 221 (3) ◽  
pp. 381-390 ◽  
Author(s):  
Gustavo W Fernandes ◽  
Cintia B Ueta ◽  
Tatiane L Fonseca ◽  
Cecilia H A Gouveia ◽  
Carmen L Lancellotti ◽  
...  
Keyword(s):  
Body Weight ◽  
Energy Expenditure ◽  
Glucose Homeostasis ◽  
High Fat Diet ◽  
Liver Steatosis ◽  
Mrna Levels ◽  
High Fat ◽  
Adaptive Thermogenesis ◽  
Brown Adipose ◽  
Similar Body

Three types of beta adrenergic receptors (ARβ1–3) mediate the sympathetic activation of brown adipose tissue (BAT), the key thermogenic site for mice which is also present in adult humans. In this study, we evaluated adaptive thermogenesis and metabolic profile of a mouse withArβ2knockout (ARβ2KO). At room temperature, ARβ2KO mice have normal core temperature and, upon acute cold exposure (4 °C for 4 h), ARβ2KO mice accelerate energy expenditure normally and attempt to maintain body temperature. ARβ2KO mice also exhibited normal interscapular BAT thermal profiles during a 30-min infusion of norepinephrine or dobutamine, possibly due to marked elevation of interscapular BAT (iBAT) and ofArβ1, andArβ3mRNA levels. In addition, ARβ2KO mice exhibit similar body weight, adiposity, fasting plasma glucose, cholesterol, and triglycerides when compared with WT controls, but exhibit marked fasting hyperinsulinemia and elevation in hepaticPepck(Pck1) mRNA levels. The animals were fed a high-fat diet (40% fat) for 6 weeks, ARβ2KO mice doubled their caloric intake, accelerated energy expenditure, and inducedUcp1expression in a manner similar to WT controls, exhibiting a similar body weight gain and increase in the size of white adipocytes to the WT controls. However, ARβ2KO mice maintain fasting hyperglycemia as compared with WT controls despite very elevated insulin levels, but similar degrees of liver steatosis and hyperlipidemia. In conclusion, inactivation of the ARβ2KO pathway preserves cold- and diet-induced adaptive thermogenesis but disrupts glucose homeostasis possibly by accelerating hepatic glucose production and insulin secretion. Feeding on a high-fat diet worsens the metabolic imbalance, with significant fasting hyperglycemia but similar liver structure and lipid profile to the WT controls.

Changes in short-term variability of blood pressure and heart rate during the development of obesity-associated hypertension in high-fat fed dogs

1999 ◽  
Vol 17 (8) ◽  
pp. 1135-1143 ◽  
Author(s):  
P Verwaerde ◽  
J M. Sénard ◽  
M Galinier ◽  
P Rougé ◽  
P Massabuau ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
High Fat ◽  
Short Term ◽  
Short Term Variability

Modulation of Sympathetic and Somatomotor Function by the Ventromedial Medulla

2004 ◽  
Vol 92 (1) ◽  
pp. 510-522 ◽  
Author(s):  
Malcolm W. Nason ◽  
Peggy Mason
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Tissue Temperature ◽  
Reticular Nucleus ◽  
Noxious Stimulation ◽  
Measured Variable ◽  
Interscapular Brown Adipose Tissue ◽  
Brown Adipose ◽  
Ventromedial Medulla ◽  
Reticular Nuclei

The ventromedial medulla is implicated in a variety of functions including nociceptive and cardiovascular modulation and the control of thermoregulation. To determine whether single microinjections into the ventromedial medulla elicit changes in one or multiple functional systems, the GABAA receptor antagonist bicuculline was microinjected (70 nl, 5–50 ng) into the ventromedial medulla of lightly anesthetized rats, and cardiovascular, respiratory, and nociceptive measures were recorded. Bicuculline microinjection into either the midline raphe or the laterally adjacent reticular nucleus simultaneously increased interscapular brown adipose tissue temperature, heart rate, blood pressure, expired [CO2], and respiration rate and elicited shivering. Bicuculline microinjection also decreased the noxious stimulus-evoked changes in heart rate and blood pressure, decreased the frequency of heat-evoked sighs, and suppressed the cortical desynchronization evoked by noxious stimulation. Although bicuculline suppressed the motor withdrawal evoked by noxious tail heat, it enhanced the motor withdrawal evoked by noxious paw heat, evidence for specifically patterned nociceptive modulation. Saline microinjections into midline or lateral sites had no effect on any measured variable. All bicuculline microinjections, midline or lateral, evoked the same set of physiological effects, consistent with the lack of a topographical organization within the ventromedial medulla. Furthermore, as predicted by the isodendritic morphology of cells in the ventromedial medulla, midline bicuculline microinjection increased the number of c-fos immunoreactive cells in both midline raphe and lateral reticular nuclei. In summary, 70-nl microinjections into ventromedial medulla activate cells in multiple nuclei and elicit increases in sympathetic and somatomotor tone and a novel pattern of nociceptive modulation.

Supernormal Left Ventricular Performance in Young Subjects with Mild Hypertension: An Alerting Response to the Echocardiographic Procedure?

1996 ◽  
Vol 91 (3) ◽  
pp. 275-281 ◽  
Author(s):  
Paolo Palatini ◽  
Pieralberto Visentin ◽  
Gianluigi Nicolosi ◽  
Vincenzo Mione ◽  
Paolo Stritoni ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Systolic Blood Pressure ◽  
Systolic Function ◽  
Blood Pressure Monitoring ◽  
Left Ventricular Systolic Function ◽  
Left Ventricular ◽  
Ventricular Performance ◽  
Young Subjects ◽  
Mild Hypertensive

1. To assess the clinical significance of supernormal left ventricular systolic function in the initial phase of hypertension, 635 never-treated 18–45-year-old borderline to mild hypertensive subjects (477 males, 158 females) were studied. All subjects underwent echocardiography, 24 h ambulatory blood pressure monitoring and 24 h urine collection for catecholamine dosage. 2. Subjects whose left ventricular shortening-stress relationship was above the 95% confidence intervals of 50 normotensive subjects of similar age and sex distribution were defined as having supernormal function. 3. Age, duration of hypertension and left ventricular mass were similar in the hypertensive subjects with normal (85%) and supernormal (15%) ejective performance. Subjects with supernormal function showed higher office systolic blood pressure (P < 0001), office heart rate (P = 0.03) and cardiac index (P < 0001). Conversely, 24 h systolic blood pressure, 24 h heart rate and 24 h catecholamine output did not differ according to left ventricular function. 4. In conclusion, the greater white-coat effect and the normal baseline sympathetic tone exhibited by the patients with increased performance suggest that supernormal left ventricular pump function is only a marker of the alerting reaction elicited by the echocardiographic examination.

Early dietary intervention: long-term effects on blood pressure, brain neuropeptide Y, and adiposity markers

2005 ◽  
Vol 288 (6) ◽  
pp. E1236-E1243 ◽  
Author(s):  
Elena Velkoska ◽  
Timothy J. Cole ◽  
Margaret J. Morris
Keyword(s):  
Blood Pressure ◽  
Body Weight ◽  
Adipose Tissue ◽  
Neuropeptide Y ◽  
Litter Size ◽  
High Fat Diet ◽  
Dietary Intervention ◽  
High Fat ◽  
Brown Adipose

Early life nutrition impacts on subsequent risk of obesity and hypertension. Several brain chemicals responsible for both feeding and cardiovascular regulation are altered in obesity. We examined effects of early postnatal overnutrition on blood pressure, brain neuropeptide Y (NPY), and adiposity markers. Rat pup litters were adjusted to either 3 or 12 male animals (overnutrition and control, respectively) on day 1 of life. After weaning, rats were given either a palatable high-fat diet or standard chow. Smaller litter pups were significantly heavier by 17 days of age. By 16 wk, the effect of litter size was masked by that of diet, postweaning. Small and normal litter animals fed a high-fat diet had similar increases in body weight, plasma insulin, leptin, and adiponectin concentrations, leptin mRNA, and fat masses relative to chow-fed animals. An increase in 11β-hydroxysteroid dehydrogenase-1 mRNA in white adipose tissue, and a decrease in uncoupling protein-1 mRNA in brown adipose tissue in both small litter groups at 16 wk of age, may represent a programming effect of the altered litter size. NPY concentration in the paraventricular nucleus of the hypothalamus was reduced in high fat-fed groups. Blood pressure was significantly elevated at 13 wk in high-fat-fed animals. This study demonstrates that overnourishment during early postnatal development leads to profound changes in body weight at weaning, which tended to abate with maturation. Thus the effects of long-term dietary intervention postweaning can override those of litter size-induced obesity.

Blood Pressure, Heart Rate and Neuroendocrine Responses to a High Carbohydrate and a High Fat Meal in Healthy Young Subjects

1990 ◽  
Vol 79 (5) ◽  
pp. 517-522 ◽  
Author(s):  
D. Heseltine ◽  
J. F. Potter ◽  
G. Hartley ◽  
I. A. MacDonald ◽  
O. F. W. James
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Plasma Insulin ◽  
The Elderly ◽  
High Fat ◽  
High Carbohydrate ◽  
Neuroendocrine Responses ◽  
Young Subjects ◽  
Fat Meal ◽  
Carbohydrate Meal

1. The responses of blood pressure, heart rate, autonomic function and plasma insulin to a high carbohydrate and a high fat meal of equivalent energy value were studied in nine young volunteers. 2. Neither meal produced a significant change in supine or erect blood pressure. The high carbohydrate meal, however, resulted in an overall rise in both supine (6 beats/min) and erect (6 beats/min; P < 0.05) heart rate, no such changes being seen after the high fat meal. 3. Plasma noradrenaline levels increased by a maximum of 126% at 90 min (0.98 to 2.22 nmol/l) after the high carbohydrate meal but were virtually unchanged after the high fat meal (P < 0.01). Parasympathetic function showed no between-meal differences. Plasma insulin and glucose levels were significantly higher after the high carbohydrate meal than after the high fat meal. No postprandial difference in packed cell volume was found between meal types. 4. We conclude that, in young subjects, the postprandial blood pressure after a high carbohydrate meal is maintained by an increase in heart rate associated with increased sympathetic nervous system activity. These changes are at variance with the blood pressure and heart rate responses seen in the elderly after a high carbohydrate meal. A high fat meal has no significant cardiovascular or neuroendocrine effects in the young or old. The nutrient composition of meals has to be taken into account when studying the postprandial cardiovascular and neuroendocrine responses in the young.

Uncoupling protein 1 expression and high-fat diets

2011 ◽  
Vol 300 (1) ◽  
pp. R1-R8 ◽  
Author(s):  
Tobias Fromme ◽  
Martin Klingenspor
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Uncoupling Protein ◽  
Caloric Intake ◽  
High Fat ◽  
Uncoupling Protein 1 ◽  
Brown Adipocytes ◽  
Adaptive Thermogenesis ◽  
Brown Adipose ◽  
Thermoregulatory Function

Uncoupling protein 1 (Ucp1) is the key component of β-adrenergically controlled nonshivering thermogenesis in brown adipocytes. This process combusts stored and nutrient energy as heat. Cold exposure not only activates Ucp1-mediated thermogenesis to maintain normothermia but also results in adaptive thermogenesis, i.e., the recruitment of thermogenic capacity in brown adipose tissue. As a hallmark of adaptive thermogenesis, Ucp1 synthesis is increased proportionally to temperature and duration of exposure. Beyond this classical thermoregulatory function, it has been suggested that Ucp1-mediated thermogenesis can also be employed for metabolic thermogenesis to prevent the development of obesity. Accordingly, in times of excess caloric intake, one may expect a positive regulation of Ucp1. The general impression from an overview of the present literature is, indeed, an increased brown adipose tissue Ucp1 mRNA and protein content after feeding a high-fat diet (HFD) to mice and rats. The reported increases are very variable in magnitude, and the effect size seems to be independent of dietary fat content and duration of the feeding trial. In white adipose tissue depots Ucp1 mRNA is generally downregulated by HFD, indicating a decline in the number of interspersed brown adipocytes.

Effects of Meal Composition on the Postprandial Blood Pressure, Catecholamine and Insulin Changes in Elderly Subjects

1989 ◽  
Vol 77 (3) ◽  
pp. 265-272 ◽  
Author(s):  
J. F. Potter ◽  
D. Heseltine ◽  
G. Hartley ◽  
J. Matthews ◽  
I. A. Macdonald ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Cell Volume ◽  
Packed Cell Volume ◽  
Plasma Insulin ◽  
Autonomic Function ◽  
High Protein ◽  
Elderly Subjects ◽  
High Fat ◽  
High Carbohydrate

1. The effects of four meals of similar energy, but different nutritional, composition on postprandial blood pressure, heart rate, autonomic function, catecholamines, insulin and packed cell volume levels were studied in seven fit elderly subjects. 2. The high carbohydrate and high protein meals led to a significant overall fall in supine systolic and diastolic blood pressure compared either with no change or a rise after the normal (i.e. mixed) and high fat meals. Similar between-meal differences were seen with erect diastolic but not erect systolic blood pressure. No significant postural blood pressure fall occurred after any of the meals. Supine heart rate was unaffected by meal type or by time, and although erect heart rate showed a small increase during the study there was no between-meal difference. 3. Parasympathetic function was unaffected by meal type. Plasma noradrenaline rose after the high carbohydrate and mixed meals only, remaining elevated for 120 min after meal consumption. This increase was not related to the changes in blood pressure or plasma insulin levels. 4. Plasma insulin and glucose rose after the high carbohydrate and mixed meals, but were unchanged after the high protein and high fat meals. Packed cell volume showed a small decrease towards the end of the study, although there was no between-meal variation. 5. The differences in the cardiovascular changes after the different meals could not be ascribed to alterations in autonomic function, insulin release or fall in plasma volume. We propose that the postprandial changes in blood pressure are due to the nutrient composition of the meal rather than the actual energy load.

Circulating resistin in lean, obese, and insulin-resistant mouse models: lack of association with insulinemia and glycemia

2005 ◽  
Vol 288 (3) ◽  
pp. E625-E632 ◽  
Author(s):  
Jennifer H. Lee ◽  
John W. Bullen ◽  
Violeta L. Stoyneva ◽  
Christos S. Mantzoros
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Mrna Expression ◽  
Mouse Models ◽  
Uncoupling Protein ◽  
High Fat ◽  
Resistant Mouse ◽  
Brown Adipose ◽  
Tnf Α ◽  
Resistin Mrna

Resistin is an adipocyte-secreted hormone proposed to link obesity with insulin resistance and diabetes, but no previous study has performed a joint quantitative evaluation of white adipose tissue (WAT) resistin mRNA expression and serum levels in relation to insulinemia and glycemia in mice. We have thus comparatively assessed WAT resistin mRNA expression and serum resistin levels in lean C57BL/6J mice and various mouse models of obesity, including diet-induced obese (DIO) C57BL/6J mice, high fat-fed TNF-α−/− mice, and brown adipose tissue (BAT)-deficient uncoupling protein-diphtheria toxin A chain (UCP1-DTA) mice. We also studied whether treatment with the weight-reducing and insulin-sensitizing compounds, MTII, an α-melanocyte-stimulating hormone analog, or CNTFAx15, a ciliary neurotrophic factor analog, alters resistin mRNA expression and/or circulating levels in lean and DIO C57BL/6J mice. We find that resistin mRNA expression is similar in DIO and lean C57BL/6J mice, as well as in TNF-α−/− and wild-type (WT) mice. Circulating resistin levels, however, are higher in DIO C57BL/6J, high fat-fed TNF-α−/−, and UCP1-DTA mice compared with lean controls. Moreover, although resistin mRNA expression is upregulated by MTII treatment for 24 h and downregulated by CNTFAx15 treatment for 3 or 7 days, circulating resistin levels are not altered by MTII or CNTFAx15 treatment. In addition, serum resistin levels, but not resistin mRNA expression levels, are correlated with body weight, and neither resistin mRNA expression nor serum resistin levels are correlated with serum insulin or glucose levels. We conclude that transcriptional regulation of resistin in WAT does not correlate with circulating resistin levels and that circulating resistin is unlikely to play a major endocrine role in insulin resistance or glycemia in mice.

Sign in / Sign up

Export Citation Format

Share Document