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BACKGROUND: Crossover studies can induce order effects, especially when they lack a wash-out period. OBJECTIVE: We performed a secondary analyses comparing groups of subjects randomized to different diet orders in two inpatient crossover studies originally designed to compare within subject differences in ad libitum energy intake. One study compared minimally processed low carbohydrate (LC) versus low fat (LF) diets and the other matched macronutrients and compared minimally processed food (MPF) versus ultra-processed food (UPF) diets. METHODS: Diet order group comparisons of changes in body weight and body composition, and differences in energy expenditure, food intake were assessed over four weeks in 20 adults randomized to either the LC followed immediately by the LF diet (LCâLF) or the opposite order (LFâLC) as well as 20 adults randomized to either the MPF followed by UPF (MPFâUPF) diets or the opposite order (UPFâMPF). RESULTS: Subjects randomized to LCâLF lost 2.9 ± 1.1 kg more body weight (p < 0.001) and 1.5 ± 0.6 kg more body fat (p = 0.03) than the LFâLC group, likely because the LCâLF group consumed 921 ± 304 kcal/d less than the LFâLC group (p = 0.003). These energy intake differences were driven by the last two weeks (-1610 ± 312 kcal/d; p < 0.0001), perhaps due to carryover effects of gut adaptations during the first two weeks arising from large differences in the mass of food (1296 ± 215 g/d; p < 0.00001) and fiber consumed (58 ± 6 g/d; p < 0.00001). There were no significant diet order effects on energy intake, body weight, or body composition changes between UPFâMPF versus MPFâUPF groups. CONCLUSIONS: Diet order significantly affected energy intake, body weight, and body fat in a 4-week crossover inpatient diet study varying in macronutrients, but not in a similarly structured study varying in ultra-processed foods. CLINICAL TRIAL REGISTRATION: NCT03407053 and NCT03878108.
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OBJECTIVE: The objective of this study was to explore how dietary macronutrient composition influences postprandial appetite hormone responses and subsequent energy intake. METHODS: A total of 20 adults (mean [SEM], age 30 [1] years, BMI 27.8 [1.3] kg/m2, n = 8 with normal weight, n = 6 with overweight, n = 6 with obesity) consumed a low-fat (LF) diet (10% fat, 75% carbohydrate) and a low-carbohydrate (LC) diet (10% carbohydrate, 75% fat) for 2 weeks each in an inpatient randomized crossover design. At the end of each diet, participants consumed isocaloric macronutrient-representative breakfast test meals, and 6-h postprandial responses were measured. Ad libitum energy intake was measured for the rest of the day. RESULTS: The LC meal resulted in greater mean postprandial plasma active glucagon-like peptide-1 (GLP-1; LC: 6.44 [0.78] pg/mL, LF: 2.46 [0.26] pg/mL; p < 0.0001), total glucose-dependent insulinotropic polypeptide (GIP; LC: 578 [60] pg/mL, LF: 319 [37] pg/mL; p = 0.0004), and peptide YY (PYY; LC: 65.6 [5.6] pg/mL, LF: 50.7 [3.8] pg/mL; p = 0.02), whereas total ghrelin (LC: 184 [25] pg/mL, LF: 261 [47] pg/mL; p = 0.0009), active ghrelin (LC: 91 [9] pg/mL, LF: 232 [28] pg/mL; p < 0.0001), and leptin (LC: 26.9 [6.5] ng/mL, LF: 35.2 [7.5] ng/mL; p = 0.01) were lower compared with LF. Participants ate more during LC at lunch (244 [85] kcal; p = 0.01) and dinner (193 [86] kcal; p = 0.04), increasing total subsequent energy intake for the day compared with LF (551 [103] kcal; p < 0.0001). CONCLUSIONS: In the short term, endogenous gut-derived appetite hormones do not necessarily determine ad libitum energy intake.
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Apetite , Estudos Cross-Over , Dieta com Restrição de Carboidratos , Dieta com Restrição de Gorduras , Ingestão de Energia , Polipeptídeo Inibidor Gástrico , Grelina , Peptídeo 1 Semelhante ao Glucagon , Peptídeo YY , Período Pós-Prandial , Humanos , Adulto , Masculino , Feminino , Peptídeo 1 Semelhante ao Glucagon/sangue , Grelina/sangue , Peptídeo YY/sangue , Polipeptídeo Inibidor Gástrico/sangue , Dieta com Restrição de Gorduras/métodos , Obesidade/sangue , Hormônios Gastrointestinais/sangue , Sobrepeso/sangue , Glicemia/metabolismo , Insulina/sangueRESUMO
Ultra-processed foods high in fat and sugar may be addictive, in part, due to their purported ability to induce an exaggerated postingestive brain dopamine response akin to drugs of abuse. Using standard [11C]raclopride positron emission tomography (PET) displacement methods used to measure brain dopamine responses to addictive drugs, we measured postingestive striatal dopamine responses to an ultra-processed milkshake high in fat and sugar in 50 young, healthy adults over a wide body mass index range (BMI 20-45 kg/m2). Surprisingly, milkshake consumption did not result in significant postingestive dopamine response in the striatum (p=0.62) nor any striatal subregion (p>0.33) and the highly variable interindividual responses were not significantly related to adiposity (BMI: r=0.076, p=0.51; %body fat: r=0.16, p=0.28). Thus, postingestive striatal dopamine responses to an ultra-processed milkshake were likely substantially smaller than many addictive drugs and below the limits of detection using standard PET methods.
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BACKGROUND: Whole-food, plant-based vegan diets, low in oils, and Mediterranean diets, rich in extra virgin olive oil (EVOO), reduce cardiovascular disease risk factors. Optimal quantity of dietary fat, particularly EVOO, is unclear. METHODS AND RESULTS: In a randomized crossover trial with weekly cooking classes, adults with ≥5% cardiovascular disease risk followed a high (4 tablespoons/day) to low (<1 teaspoon/day) or low to high EVOO whole-food, plant-based diet for 4 weeks each, separated by a 1-week washout. The primary outcome was difference in low-density lipoprotein cholesterol (LDL-C) from baseline. Secondary measures were changes in additional cardiometabolic markers. Linear mixed models assessed changes from baseline between phases, with age, sex, and body weight change as covariates. In 40 participants, fat intake comprised 48% and 32% of energy during high and low EVOO phases, respectively. Both diets resulted in comparable reductions in LDL-C, total cholesterol, apolipoprotein B, high-density lipoprotein cholesterol, glucose, and high-sensitivity C-reactive protein (all P<0.05). With diet-sequence interactions for LDL-C, differences were detected between diets by diet order (mean±SEM high to low: Δ-12.7[5.9] mg/dL, P=0.04 versus low to high: Δ+15.8[6.8] mg/dL, P=0.02). Similarly, low to high order led to increased glucose, total cholesterol, and high-density lipoprotein cholesterol (all P<0.05). Over period 1, LDL-C reductions were -25.5(5.1) post-low versus -16.7(4.2) mg/dL post-high EVOO, P=0.162, which diminished over period 2. CONCLUSIONS: Both plant-based diet patterns improved cardiometabolic risk profiles compared with baseline diets, with more pronounced decreases in LDL-C after the low EVOO diet. Addition of EVOO after following a low intake pattern may impede further lipid reductions. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04828447.
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Doenças Cardiovasculares , LDL-Colesterol , Estudos Cross-Over , Dieta Vegana , Azeite de Oliva , Humanos , Azeite de Oliva/administração & dosagem , Masculino , Feminino , Pessoa de Meia-Idade , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/epidemiologia , LDL-Colesterol/sangue , Adulto , Fatores de Risco Cardiometabólico , Idoso , Biomarcadores/sangue , Dieta VegetarianaAssuntos
Resistência à Insulina , Insulina , Humanos , Obesidade , Carboidratos , Insulina Regular Humana , Carboidratos da Dieta , GlicemiaRESUMO
BACKGROUND: Crossover studies can induce order effects, especially when they lack a wash-out period. OBJECTIVE: To explore diet order effects on energy balance and food intake between randomized diet order groups in two inpatient crossover studies originally designed to compare within-subject differences in ad libitum energy intake between either minimally processed low carbohydrate (LC) versus low fat (LF) diets or macronutrient-matched diets composed of mostly minimally processed food (MPF) or ultra-processed food (UPF). METHODS: Diet order group comparisons of changes in body weight, body composition, and differences in energy expenditure, and food intake were assessed over four weeks in 20 adults randomized to either the LC followed immediately by the LF diet (LCâLF) or the opposite order (LFâLC) as well as 20 adults randomized to either the MPF followed by UPF (MPFâUPF) diets or the opposite order (UPFâMPF). RESULTS: Subjects randomized to LCâLF lost 2.9 ± 1.1 kg more body weight (p < 0.001) and 1.5 ± 0.6 kg more body fat (p = 0.03) than the LFâLC group likely because the LCâLF group consumed 922 ± 304 kcal/d less than the LFâLC group (p = 0.0024). Reduced energy intake in LCâLF vs LFâLC was driven by the last two weeks (-1610 ± 306 kcal/d; p<0.00001) perhaps due to carryover effects of gut adaptations over the first two weeks arising from large differences in the mass of food (1295 ± 209 g/d; p<0.00001) and fiber intake (58 ± 5 g/d; p<0.00001). There were no diet order effects on ad libitum energy intake, body weight, or body composition change between UPFâMPF versus MPFâUPF groups. CONCLUSIONS: Diet order influences daily ad libitum energy intake, body weight change, and fat change within the context of a 4-week crossover inpatient diet study varying in macronutrients, but not varying in extent and purpose of processing. Funding sources: Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. Clinical Trial Registration: NCT03407053 and NCT03878108.
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The relationship between adiposity and dopamine type-2 receptor binding potential (D2BP) in the human brain has been repeatedly studied for >20 years with highly discrepant results, likely due to variable methodologies and differing study populations. We conducted a controlled inpatient feeding study to measure D2BP in the striatum using positron emission tomography with both [18F]fallypride and [11C]raclopride in pseudo-random order in 54 young adults with a wide range of body mass index (BMI 20-44 kg/m2). Within-subject D2BP measurements using the two tracers were moderately correlated (r=0.47, p<0.001). D2BP was negatively correlated with BMI as measured by [11C]raclopride (r= -0.51; p<0.0001) but not [18F]fallypride (r=-0.01; p=0.92) and these correlation coefficients were significantly different from each other (p<0.001). Given that [18F]fallypride has greater binding affinity to dopamine type-2 receptors than [11C]raclopride, which is more easily displaced by endogenous dopamine, our results suggest that adiposity is positively associated with increased striatal dopamine tone.
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Gut-derived hormones affect appetite and are thought to play an important role in body weight regulation. Dietary macronutrient composition can influence gut-derived appetite hormone concentrations, thereby providing theoretical basis for why some diets might facilitate weight loss better than others. We investigated postprandial gut-derived appetite hormones in 20 inpatient adults after 2 weeks of eating either a low carbohydrate (LC) or a low fat (LF) diet followed by the alternate diet in random order. A LC meal resulted in significantly greater postprandial GLP-1, GIP, and PYY but lower ghrelin compared to an isocaloric LF meal (all p≤0.02). However, differences in gut-derived appetite hormones were incommensurate with subsequent ad libitum energy intake over the rest of the day, which was 551±103 kcal (p<0.0001) greater with the LC as compared to the LF diet. The effects of gut-derived appetite hormones on ad libitum energy intake can be dominated by other diet-related factors, at least in the short-term.
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Background: Continuous glucose monitors (CGMs) are being used to characterize postprandial glycemic responses and thereby provide personalized dietary advice to minimize glycemic excursions. However, the efficacy of such advice depends on reliable CGM responses. Objective: To explore within-subject variability of CGM responses to duplicate meals in an inpatient setting. Methods: CGM data were collected in two controlled feeding studies (NCT03407053 and NCT03878108) in 30 participants without diabetes capturing 1056 meal responses in duplicate ~1 week apart from four dietary patterns. One study used two different CGMs (Abbott Freestyle Libre Pro and Dexcom G4 Platinum) whereas the other study used only Dexcom. We calculated the incremental area under the curve (iAUC) for each 2-h post-meal period and compared within-subject iAUCs using the same CGM for the duplicate meals using linear correlations, intra-class correlation coefficients (ICC), Bland-Altman analyses, and compared individual variability of glycemic responses to duplicate meals versus different meals using standard deviations (SDs). Results: There were weak to moderate positive linear correlations between within- subject iAUCs for duplicate meals (Abbott r=0.47, p<0.0001, Dexcom r=0.43, p<0.0001), with low within-participant reliability indicated by ICC (Abbott 0.31, Dexcom 0.14). Bland-Altman analyses indicated wide limits of agreement (Abbott -31.3 to 31.5 mg/dL, Dexcom -30.8 to 30.4 mg/dL) but no significant bias of mean iAUCs for duplicate meals (Abbott 0.1 mg/dL, Dexcom -0.2 mg/dL). Individual variability of glycemic responses to duplicate meals was similar to that of different meals evaluated each diet week for both Abbott (SDduplicate = 10.7 mg/dL , SDweek 1 =12.4 mg/dL, SDweek 2 =11.6 mg/dL, p=0.38) and Dexcom (SDduplicate = 11.1 mg/dL, SDweek 1 = 11.5 mg/dL, SDweek 2 =11.9 mg/dL, p=0.60). Conclusions: Individual postprandial CGM responses to duplicate meals were unreliable in adults without diabetes. Personalized diet advice based on CGM measurements in adults without diabetes requires more reliable methods involving aggregated repeated measurements.
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BACKGROUNDWeight-loss diets often target dietary fat or carbohydrates, macronutrients that are sensed via distinct gut-brain pathways and differentially affect peripheral hormones and metabolism. However, the effects of such diet changes on the human brain are unclear. METHODSWe investigated whether selective isocaloric reductions in dietary fat or carbohydrates altered dopamine D2/3 receptor binding potential (D2BP) and neural activity in brain-reward regions in response to visual food cues in 17 inpatient adults with obesity as compared with a eucaloric baseline diet using a randomized crossover design. RESULTSOn the fifth day of dietary fat restriction, but not carbohydrate restriction, both D2BP and neural activity to food cues were decreased in brain-reward regions. After the reduced-fat diet, ad libitum intake shifted toward foods high in both fat and carbohydrates. CONCLUSIONThese results suggest that dietary fat restriction increases tonic dopamine in brain-reward regions and affects food choice in ways that may hamper diet adherence. TRIAL REGISTRATIONClinicalTrials.gov NCT00846040 FUNDING. NIDDK 1ZIADK013037.
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Gorduras na Dieta , Dopamina , Adulto , Humanos , Estudos Cross-Over , Encéfalo , NutrientesRESUMO
Diets for the prevention and treatment of obesity are often informed by theories about food characteristics believed to support spontaneous reductions in ad libitum energy intake without inducing hunger. Here we estimated how energy density, hyper-palatability, protein content and eating rate affected ad libitum energy intake of 2,733 meals from four dietary patterns. Energy density, eating rate and hyper-palatable foods were consistently positively related to meal energy intake across all diets. Protein content was positively related to meal energy intake during ultraprocessed and unprocessed diets but was not significantly related to energy intake of minimally processed low-fat or low-carbohydrate meals.
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Gorduras na Dieta , Ingestão de Energia , Humanos , Obesidade/prevenção & controle , Refeições , Dieta com Restrição de GordurasRESUMO
OBJECTIVE: Physical activity is a major component of total energy expenditure (TEE) that exhibits extreme variability in mice. Our objective was to construct a general, physiology-based model of TEE to accurately quantify the energy cost of physical activity. METHODS: Spontaneous home cage physical activity, body temperature, TEE, and energy intake were measured with frequent sampling. The energy cost of activity was modeled considering six contributors to TEE (basal metabolic rate, thermic effect of food, body temperature, cold induced thermogenesis, physical activity, and body weight). An ambient temperature of 35 °C was required to remove the contribution from cold induced thermogenesis. Basal metabolic rate was adjusted for body temperature using a Q10 temperature coefficient. RESULTS: We developed a TEE model that robustly explains 70-80% of the variance in TEE at 35 °C while fitting only two parameters, the basal metabolic rate and the mass-specific energy cost per unit of physical activity, which averaged 60 cal/km/g body weight. In Ucp1-/- mice the activity cost was elevated by 60%, indicating inefficiency and increased muscle thermogenesis. The diurnal rhythm in TEE was quantitatively explained by the combined diurnal differences in physical activity, body temperature, and energy intake. Incorporating body temperature into human basal metabolic rate measurements significantly reduced the inter-individual variation. CONCLUSIONS: The physiology-based model of TEE allows quantifying the energy cost of physical activity. While applied here to mice, the model should be generally valid across species. Due to the effect of body temperature, we suggest that basal metabolic rate measurements be corrected to a reference body temperature, including in humans. Having an accurate cost of physical activity allows mechanistic dissection of disorders of energy homeostasis, including obesity.
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Metabolismo Basal , Metabolismo Energético , Humanos , Animais , Camundongos , Metabolismo Energético/fisiologia , Peso Corporal/fisiologia , Metabolismo Basal/fisiologia , Obesidade , Termogênese/fisiologiaRESUMO
Ultra-processed food consumption has increased worldwide, yet little is known about the potential links with taste preference and sensitivity. This exploratory study aimed to (i) compare sweet and salty taste detection thresholds and preferences following consumption of ultra-processed and unprocessed diets, (ii) investigate whether sweet and salty taste sensitivity and preference were associated with taste substrates (i.e. sodium and sugar) and ad libitum nutrient intake, and (iii) examine associations of taste detection thresholds and preferences with blood pressure (BP) and anthropometric measures following consumption of ultra-processed and unprocessed diets. In a randomized crossover study, participants (N = 20) received ultra-processed or unprocessed foods for 2 weeks, followed by the alternate diet. Baseline food intake data were collected prior to admission. Taste detection thresholds and preferences were measured at the end of each diet arm. Taste-substrate/nutrient intake, body mass index (BMI), and body weight (BW) were measured daily. No significant differences were observed in participant salt and sweet detection thresholds or preferences after 2 weeks on ultra-processed or unprocessed diets. There was no significant association between salt and sweet taste detection thresholds, preferences, and nutrient intakes on either diet arm. A positive correlation was observed between salt taste preference and systolic BP (r = 0.59; P = 0.01), BW (r = 0.47, P = 0.04), and BMI (r = 0.50; P = 0.03) following consumption of the ultra-processed diet. Thus, a 2-week consumption of an ultra-processed diet does not appear to acutely impact sweet or salty taste sensitivity or preference. Trial Registration: ClinicalTrials.gov Identifier NCT03407053.
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Preferências Alimentares , Paladar , Humanos , Estudos Cross-Over , Projetos Piloto , Dieta , Ingestão de Energia , Peso CorporalRESUMO
Obesity and its consequences are among the greatest challenges in healthcare. The gut microbiome is recognized as a key factor in the pathogenesis of obesity. Using a mouse model, we show here that a wild-derived microbiome protects against excessive weight gain, severe fatty liver disease and metabolic syndrome during a 10-week course of high-fat diet. This phenotype is transferable only during the first weeks of life. In adult mice, neither transfer nor severe disturbance of the wild-type microbiome modifies the metabolic response to a high-fat diet. The protective phenotype is associated with increased secretion of metabolic hormones and increased energy expenditure through activation of brown adipose tissue. Thus, we identify a microbiome that protects against weight gain and its negative consequences through metabolic programming in early life. Translation of these results to humans may identify early-life therapeutics that protect against obesity.
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Dieta , Resistência à Doença , Suscetibilidade a Doenças , Exposição Ambiental , Interações entre Hospedeiro e Microrganismos , Microbiota , Obesidade/etiologia , Ração Animal , Animais , Dieta/efeitos adversos , Dieta Hiperlipídica , Modelos Animais de Doenças , Metabolismo Energético , Microbioma Gastrointestinal , Camundongos , Fatores de Tempo , Aumento de PesoRESUMO
The carbohydrate-insulin model of obesity posits that high-carbohydrate diets lead to excess insulin secretion, thereby promoting fat accumulation and increasing energy intake. Thus, low-carbohydrate diets are predicted to reduce ad libitum energy intake as compared to low-fat, high-carbohydrate diets. To test this hypothesis, 20 adults aged 29.9 ± 1.4 (mean ± s.e.m.) years with body mass index of 27.8 ± 1.3 kg m-2 were admitted as inpatients to the National Institutes of Health Clinical Center and randomized to consume ad libitum either a minimally processed, plant-based, low-fat diet (10.3% fat, 75.2% carbohydrate) with high glycemic load (85 g 1,000 kcal-1) or a minimally processed, animal-based, ketogenic, low-carbohydrate diet (75.8% fat, 10.0% carbohydrate) with low glycemic load (6 g 1,000 kcal-1) for 2 weeks followed immediately by the alternate diet for 2 weeks. One participant withdrew due to hypoglycemia during the low-carbohydrate diet. The primary outcomes compared mean daily ad libitum energy intake between each 2-week diet period as well as between the final week of each diet. We found that the low-fat diet led to 689 ± 73 kcal d-1 less energy intake than the low-carbohydrate diet over 2 weeks (P < 0.0001) and 544 ± 68 kcal d-1 less over the final week (P < 0.0001). Therefore, the predictions of the carbohydrate-insulin model were inconsistent with our observations. This study was registered on ClinicalTrials.gov as NCT03878108 .
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Metabolismo Energético/fisiologia , Insulina/metabolismo , Obesidade/metabolismo , Sobrepeso/metabolismo , Adulto , Composição Corporal , Índice de Massa Corporal , Dieta com Restrição de Gorduras/efeitos adversos , Dieta Cetogênica/efeitos adversos , Dieta Vegetariana/efeitos adversos , Carboidratos da Dieta/metabolismo , Gorduras na Dieta/metabolismo , Ingestão de Energia , Feminino , Humanos , Insulina/genética , Masculino , Pessoa de Meia-Idade , Obesidade/dietoterapia , Obesidade/epidemiologia , Obesidade/patologia , Sobrepeso/dietoterapia , Sobrepeso/epidemiologia , Redução de PesoRESUMO
BACKGROUND: High postprandial glucose excursions may increase risk for disease. Individuals have widely varying glucose responses to different meals, and precision nutrition approaches often seek to personalize diets to minimize postprandial glycemic responses as measured by continuous glucose monitors (CGMs). However, it is unknown whether different CGM devices result in concordant meal rankings according to postprandial glycemic excursions. OBJECTIVE: We explored whether meal rankings according to postprandial glycemic excursions differ between 2 simultaneously worn CGMs. METHODS: We collected 27,489 simultaneous measurements from Dexcom G4 Platinum and Abbott Freestyle Libre Pro CGMs during 28 inpatient days in 16 adults without diabetes. Simultaneous glucose measurements obtained for 2 h following 760 ad libitum meals were used to compare within-subject meal rankings between the CGM devices according to their incremental glucose response. RESULTS: Postprandial responses to ad libitum meals were highly variable, with the Abbott and Dexcom systems resulting in within-subject incremental mean ± SD glucose CVs of 91.7 ± 1.9% and 94.2 ± 2.7%, respectively. Within-subject meal rankings for incremental glycemic responses were relatively discordant between CGMs, with a mean Kendall rank correlation coefficient of 0.43 ± 0.05. Meals in the bottom compared with those in the top half of incremental glycemic responses ranked by Abbott resulted in 50 ± 10% (P = 0.0002) less glycemic reduction as measured by Dexcom, and vice versa. The missing glycemic reduction by eating meals ranked according to the discordant CGM was inversely correlated with each subject's Kendall rank correlation coefficient (r = -0.95; P < 0.0001). CONCLUSIONS: Precision nutrition approaches that use CGMs to personalize meal recommendations for minimizing glycemic excursions may be premature given the discordance of within-subject meal rankings between simultaneous CGM devices. More research is needed to clarify the source of this imprecision. This trial was registered at clinicaltrials.gov as NCT03407053.
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Glicemia/análise , Estado Nutricional , Período Pós-Prandial/fisiologia , Medicina de Precisão , Adulto , Feminino , Humanos , Masculino , Refeições , Ciências da NutriçãoRESUMO
Understanding mouse thermal physiology informs the usefulness of mice as models of human disease. It is widely assumed that the mouse tail contributes greatly to heat loss (as it does in rat), but this has not been quantitated. We studied C57BL/6J mice after tail amputation. Tailless mice housed at 22°C did not differ from littermate controls in body weight, lean or fat content, or energy expenditure. With acute changes in ambient temperature from 19 to 39°C, tailless and control mice demonstrated similar body temperatures (Tb), metabolic rates, and heat conductances and no difference in thermoneutral point. Treatment with prazosin, an α1-adrenergic antagonist and vasodilator, increased tail temperature in control mice by up to 4.8 ± 0.8°C. Comparing prazosin treatment in tailless and control mice suggested that the tail's contribution to total heat loss was a nonsignificant 3.4%. Major heat stress produced by treatment at 30°C with CL316243, a ß3-adrenergic agonist, increased metabolic rate and Tb and, at a matched increase in metabolic rate, the tailless mice showed a 0.72 ± 0.14°C greater Tb increase and 7.6% lower whole body heat conductance. Thus, the mouse tail is a useful biomarker of vasodilation and thermoregulation, but in our experiments contributes only 5-8% of whole body heat dissipation, less than the 17% reported for rat. Heat dissipation through the tail is important under extreme scenarios such as pharmacological activation of brown adipose tissue; however, non-tail contributions to heat loss may have been underestimated in the mouse.
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Regulação da Temperatura Corporal/fisiologia , Modelos Animais , Cauda/fisiologia , Antagonistas de Receptores Adrenérgicos alfa 1 , Amputação Cirúrgica , Animais , Composição Corporal/fisiologia , Superfície Corporal , Regulação da Temperatura Corporal/efeitos dos fármacos , Peso Corporal/fisiologia , Metabolismo Energético/fisiologia , Resposta ao Choque Térmico , Camundongos , Camundongos Endogâmicos C57BL , Prazosina/farmacologia , Ratos , Cauda/cirurgia , Vasodilatação/fisiologiaRESUMO
Human and mouse thermal physiology differ due to dissimilar body sizes. Unexpectedly, in mice we found no ambient temperature zone where both metabolic rate and body temperature were constant. Body temperature began increasing once cold-induced thermogenesis was no longer required. This result reproduced in male, female, C57BL/6J, 129, chow-fed, diet-induced obese, and ob/ob mice as well as Trpv1-/-;Trpm8-/-;Trpa1-/- mice lacking thermal sensory channels. During the resting-light phase, the energy expenditure minimum spanned â¼4°C of ambient temperature, whereas in the active-dark phase it approximated a point. We propose the concept of a thermoneutral point (TNP), a discrete ambient temperature below which energy expenditure increases and above which body temperature increases. Humans do not have a TNP. As studied, the mouse TNP is â¼29°C in light phase and â¼33°C in dark phase. These observations inform how thermoneutrality is defined and how mice are used to model human energy physiology and drug development.