scholarly journals Divergent Energy Expenditure Impacts Mouse Metabolic Adaptation to Acute High-Fat/High-Sucrose Diet Producing Sexually Dimorphic Weight Gain Patterns

2019 ◽  
Author(s):  
E. Matthew Morris ◽  
Roberto D. Noland ◽  
Julie A. Allen ◽  
Colin S. McCoin ◽  
Qing Xia ◽  
...  

ABSTRACTObjectiveLong-term weight gain can result from cumulative small weight increases due to short-term excess caloric intake during weekends and holidays. Increased physical activity may mediate weight gain through increases in energy expenditure (EE) and reductions in energy balance. Current methods for modulating mouse EE (e.g. – exercise, chemical uncouplers, etc.) have confounding effects. However, it is known that mouse EE linearly increases as housing temperature decreases below the thermoneutral zone.MethodsTo determine how robust differences in baseline EE impact 7-day changes in weight and body composition on low-fat and high-fat, high-sucrose (HFHS) diets, we performed indirect calorimetry measurements in male and female mice housed at divergent temperatures (20°C vs. 30°C).ResultsAs expected, mice housed at 30°C have ∼40% lower total EE and energy intake compared to 20°C mice regardless of diet or sex. Energy balance was increased with HFHS in all groups, with ∼30% greater increases observed in 30°C versus 20°C mice. HFHS increased weight gain regardless of temperature or sex. Interestingly, no HFHS-induced weight gain differences were observed between females at different temperatures. In contrast, 30°C male mice on HFHS gained ∼50% more weight than 20°C males, and ∼80% more weight compared to 30°C females. HFHS increased fat mass across all groups but 2-fold higher gains occurred in 30°C mice compared to 20°C mice. Females gained ∼35% less fat mass than males at both temperatures.ConclusionsTogether, these data reveal an interaction between divergent ambient temperature-induced EE and sex that impacted diet-induced patterns of short-term weight gain and body composition.HighlightsUtilized ambient temperature differences as an experimental tool to study the impact of divergent baseline energy expenditure on metabolic adaptation to high-fat, high-sucrose diet.Baseline energy expenditure and sex interact to impact diet-induced changes in body composition and weight gain.The energy expenditure and sex interaction is a result of an inverse relationship between fat mass gain and weight-adjusted total energy expenditure, as well as, diet-induced non-shivering thermogenesis.These data support that the hypothesis that higher energy expenditure amplifies the coupling of energy intake to energy expenditure during energy dense feeding, resulting in reduced positive energy balance and reduced gains in weight and adiposity.First evidence that energy expenditure level plays a role in the composition of weight gained by female mice during acute HFHS feeding.This study further highlights issues with obesity/energy metabolism research performed in mice at sub-thermoneutral housing temperatures, particularly with sex comparisons.GRAPHIC ABSTRACTLegend: Male and female mice housed at 30°C had lower energy expenditure (EE) & energy intake (EI), while having greater energy balance (EB), during 7-day high-fat/high-sucrose (HFHS) feeding compared to male and female mice, respectively, housed at 20°C. However, female mice had lower EB compared to males at both housing temperature. Female mice housed at 30°C gained less weight than 30°C males but gained the same relative amount of fat mass during acute HFHS feeding. Interestingly, 20°C females gained the same amount of weight as 20°C males but gained primarily fat-free mass, while the males gained the same proportion of fat as 30°C males and females.

2010 ◽  
Vol 299 (4) ◽  
pp. R1097-R1105 ◽  
Author(s):  
Matthew R. Jackman ◽  
Paul S. MacLean ◽  
Daniel H. Bessesen

While most rats gain weight when placed on a high-fat diet (HFD), some strains resist HFD-induced weight gain. To maintain weight, obesity-resistant (OR) rats must either eat less than obesity-prone (OP) rats or increase total energy expenditure (TEE). To determine if changes in TEE predispose to or protect from weight gain, energy expenditure, energy intake, and weight gain were measured in male and female OP and OR rats consuming a low-fat diet (LFD) and for 5 days after switching to a HFD. After 5 days on a HFD, OP rats gained significantly more weight (male: 42.8 ± 6.9 g, female: 25.5 ± 3.0 g) than their OR counterparts (male: 24.0 ± 7.5 g, female: 13.7 ± 1.4 g). Both male and female rats significantly increased their energy intake when transitioned to the HFD, and TEE increased modestly in all groups. Compared with female OP rats, female OR rats had a significantly greater increase in TEE on the HFD. This was due to an increase in both resting and nonresting energy expenditure. In contrast, the effect of the HFD in males was minor. TEE was also measured in female rats consuming a HFD, pair fed to LFD calories. The increase in TEE of pair-fed female OR rats was substantially less than what was seen in the HFD ad libitum condition. Physical activity was also measured in female rats. There was no evidence that increases in physical activity were the cause of the increased TEE seen in female OR rats consuming a HFD. These results suggest that resistance to HFD-induced weight gain in female OR rats may be due in part to an increase in TEE and a greater reliance on lipid as an energy source. Changes in TEE appear to be triggered by overconsumption of the HFD and not simply the diet composition.


Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 1999-P ◽  
Author(s):  
HYE LIM NOH ◽  
SUJIN SUK ◽  
RANDALL H. FRIEDLINE ◽  
KUNIKAZU INASHIMA ◽  
DUY A. TRAN ◽  
...  

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A806-A806
Author(s):  
Rachel Bell ◽  
Elisa Villalobos ◽  
Mark Nixon ◽  
Allende Miguelez-Crespo ◽  
Matthew Sharp ◽  
...  

Abstract Glucocorticoids play a critical role in metabolic homeostasis. Chronic or excessive activation of the glucocorticoid receptor (GR) in adipose tissue contributes to metabolic disorders such as glucose intolerance and insulin resistance. Steroid-metabolising enzymes in adipose, such as 11β-HSD1 or 5α-reductase, modulate the activation of GR by converting primary glucocorticoids into more or less potent ligands. Carbonyl reductase 1 (CBR1) is a novel regulator of glucocorticoid metabolism, converting corticosterone/cortisol to 20β-dihydrocorticosterone/cortisol (20β-DHB/F); a metabolite which retains GR activity. CBR1 is abundant in adipose tissue and increased in obese adipose of mice and humans1 and increased Cbr1 expression is associated with increased fasting glucose1. We hypothesised that increased Cbr1/20β-DHB in obese adipose contributes to excessive GR activation and worsens glucose tolerance. We generated a novel murine model of adipose-specific Cbr1 over-expression (R26-Cbr1Adpq) by crossing conditional knock-in mice with Adiponectin-Cre mice. CBR1 protein and activity were doubled in subcutaneous adipose tissue of male and female R26-Cbr1Adpq mice compared with floxed controls; corresponding to a two-fold increase 20β-DHB (1.6 vs. 4.2ng/g adipose; P=0.0003; n=5-7/group). There were no differences in plasma 20β-DHB or corticosterone. Bodyweight, lean or fat mass, did not differ between male or female R26-Cbr1Adpq mice and floxed controls. Lean male R26-Cbr1Adpq mice had higher fasting glucose (9.5±0.3 vs. 8.4±0.3mmol/L; P=0.04) and worsened glucose tolerance (AUC 1819±66 vs. 1392±14; P=0.03). Female R26-Cbr1Adpq mice also had a worsened glucose tolerance but fasting glucose was not altered with genotype. There were no differences in fasting insulin or non-esterified fatty acid between genotypes in either sex. Expression of GR-induced genes Pnpla2, Gilz and Per1, were increased in adipose of R26-Cbr1Adpq mice. Following high-fat diet induced obesity, no differences in bodyweight, lean or fat mass, with genotype were observed in male and female mice, and genotype differences in fasting glucose and glucose tolerance were abolished. In conclusion, adipose-specific over-expression of Cbr1 in lean male and female mice led to increased levels of 20β-DHB in adipose but not plasma, and both sexes having worsened glucose tolerance. The influence of adipose CBR1/20β-DHB on glucose tolerance was not associated with altered fat mass or bodyweight and was attenuated by high-fat diet-induced obesity. These metabolic consequences of Cbr1 manipulation require careful consideration given the wide variation in CBR1 expression in the human population, the presence of inhibitors and enhancers in many foodstuffs and the proposed use of inhibitors as an adjunct for cancer treatment regimens. Reference: Morgan et al., Scientific Reports. 2017; 7.


Circulation ◽  
2013 ◽  
Vol 127 (suppl_12) ◽  
Author(s):  
Gregory A Hand ◽  
Robin P Shook ◽  
Jason R Jaggers ◽  
Amanda Paluch ◽  
Vivek K Prasad ◽  
...  

Conversion, utilization and storage of energy in the regulation of energy balance is poorly understood. These misconceptions arise from confusion related to energy balance and its impact on body weight and composition, and can bias the interpretation of findings that are important for the development of policies addressing the obesity epidemic. PURPOSE: Our purpose was to examine the regulation of interactions between total daily energy intake (TDEI) and energy expenditure (TDEE) in healthy adults. METHODS: Adults not limited by gender, race or ethnicity (n=430; aged 21 to 40; BMI of 20 to 35) participated in a battery of physiological, anthropomorphic, behavioral and psychological measurements that are associated with energy balance regulation. The primary components of energy balance regulation (TDEI and TDEE) were measured by 3 random 24-hour dietary recalls and SenseWear accelerometry, respectively. Body composition was determined by dual x-ray absorptiometry (DXA). Absolute and relative resting metabolic rates (aRMR and rRMR) were determined through hooded indirect calorimetry. General linear modeling was used to examine the relationships of weight and body fatness with TDEI and macronutrient composition as well as the largest components of TDEE including aRMR, rRMR and physical activity energy expenditure (PAEE). In addition, data were compared between participants with a healthy body fat % (below 25; n=123) and obese (at or above 30%; n=241). RESULTS: All results were adjusted for age, gender and race. TDEE was positively associated (r=.47, p<.001) with TDEI. There was a positive association between aRMR (L/min) and weight (r=.743, p<.001). By contrast, rRMR (ml/kg/min) was inversely correlated with body weight (r= -.38; p<.001). TDEI was significantly higher in the lean group (2465±66 to 1878±42, p<.001) with no measureable differences in macronutrient percentages. The lean group had a higher TDEE and PAEE as compared to the obese group. CONCLUSIONS: There was a robust matching of TDEI and TDEE across weight and body composition ranges. Heavy people burned more calories than lighter people although the lighter individuals had a higher rRMR. The leaner group had a higher TDEI, reflecting a potential regulation based on the greater TDEE in this group. Further, the increased TDEE could be explained by the higher PAEE (approximately 500 kcal) in leaner individuals. These findings emphasize that energy expenditure is related to mass rather than body composition. The regulation of energy intake and body composition is multifactorial, with PAEE a significant determinant for energy storage. This study was funded through an unrestricted grant from The Coca-Cola Company.


2019 ◽  
Vol 44 (2) ◽  
pp. 172-178 ◽  
Author(s):  
Matthew M. Schubert ◽  
Elyse A. Palumbo

CrossFit (CF; CrossFit Inc., Washington, DC, USA) is a form of high-intensity functional training that focuses on training across the entire spectrum of physical fitness. CF has been shown to improve a number of indicators of health but little information assessing energy balance exists. The purpose of the present study was to investigate energy balance during 1 week of CF training. Men and women (n = 21; mean ± SD; age, 43.5 ± 8.4 years; body mass index, 27.8 ± 4.9 kg·m−2), with ≥3 months CF experience, had body composition assessed via air displacement plethysmography before and after 1 week of CF training. Participants wore ActiHeart monitors to assess total energy expenditure (TEE), activity energy expenditure, and CF energy expenditure (CF EE). Energy intake was assessed from TEE and Δ body composition. CF EE averaged 605 ± 219 kcal per 72 ± 10 min session. Weekly CF EE was 2723 ± 986 kcal. Participants were in an energy deficit (TEE: 3674 ± 855 kcal·day−1; energy intake: 3167 ± 1401 kcal·day−1). Results of the present study indicate that CF training can account for a significant portion of daily activity energy expenditure. The weekly expenditure is within levels shown to induce clinically meaningful weight loss in overweight/obese populations.


2015 ◽  
Vol 4 ◽  
Author(s):  
S. Ware ◽  
J.-P. Voigt ◽  
S. C. Langley-Evans

AbstractFetal exposure to maternal undernutrition has lifelong consequences for physiological and metabolic function. Maternal low-protein diet is associated with an age-related phenotype in rats, characterised by a period of resistance to development of obesity in early adulthood, giving way to an obesity-prone, insulin-resistant state in later adulthood. Offspring of rats fed a control (18 % casein) or low-protein (9 % casein; LP) diet in pregnancy were challenged with a high-fat diet at 9 months of age. To assess whether other maternal factors modulated the programming effects of nutrition, offspring were studied from young (2–4 months old) and older (6–9 months old) mothers. Weight gain with a high-fat diet was attenuated in male offspring of older mothers fed LP (interaction of maternal age and diet; P = 0·011) and adipose tissue deposition was lower with LP feeding in both males and females (P < 0·05). Although the resistance to weight gain and adiposity was partially explained by lower energy intake in offspring of LP mothers (P < 0·001 males only), it was apparent that energy expenditure must be influenced by maternal diet and age. Assessment of locomotor activity indicated that energy expenditure associated with physical activity was unlikely to explain resistance to weight gain, but showed that offspring of older mothers were more anxious than those of younger mothers, with more rearing observed in a novel environment and on the elevated plus-maze. The data showed that in addition to maternal undernutrition, greater maternal age may influence development and long-term body composition in the rat.


2018 ◽  
Vol 50 (8) ◽  
pp. 605-614
Author(s):  
Hong He ◽  
Katie Holl ◽  
Sarah DeBehnke ◽  
Chay Teng Yeo ◽  
Polly Hansen ◽  
...  

Type 2 diabetes is a complex disorder affected by multiple genes and the environment. Our laboratory has shown that in response to a glucose challenge, two-pore channel 2 ( Tpcn2) knockout mice exhibit a decreased insulin response but normal glucose clearance, suggesting they have improved insulin sensitivity compared with wild-type mice. We tested the hypothesis that improved insulin sensitivity in Tpcn2 knockout mice would protect against the negative effects of a high fat diet. Male and female Tpcn2 knockout (KO), heterozygous (Het), and wild-type (WT) mice were fed a low-fat (LF) or high-fat (HF) diet for 24 wk. HF diet significantly increases body weight in WT mice relative to those on the LF diet; this HF diet-induced increase in body weight is blunted in the Het and KO mice. Despite the protection against diet-induced weight gain, however, Tpcn2 KO mice are not protected against HF-diet-induced changes in glucose or insulin area under the curve during glucose tolerance tests in female mice, while HF diet has no significant effect on glucose tolerance in the male mice, regardless of genotype. Glucose disappearance during an insulin tolerance test is augmented in male KO mice, consistent with our previous findings suggesting enhanced insulin sensitivity in these mice. Male KO mice exhibit increased fasting plasma total cholesterol and triglyceride concentrations relative to WT mice on the LF diet, but this difference disappears in HF diet-fed mice where there is increased cholesterol and triglycerides across all genotypes. These data demonstrate that knockout of Tpcn2 may increase insulin action in male, but not female, mice. In addition, both male and female KO mice are protected against diet-induced weight gain, but this protection is likely independent from glucose tolerance, insulin sensitivity, and plasma lipid levels.


2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 503-503
Author(s):  
Zhiji Huang ◽  
Yafang Ma ◽  
Chunbao Li

Abstract Objectives Kappa-Carrageenan(CGN) is a widely used food additive in the meat industry and a highly viscous soluble dietary fiber which can hardly be fermented. It has been shown to be able to regulate the energy metabolism and inhibit diet-induced obesity. However, the mechanism is not well understood. The purpose of this study is to investigate the mechanisms of κ-carrageenan to inhibit the body weight gain. Methods A high-fat diet incorporated with lard, pork protein and CGN (2% or 4%, w/w) was given to C57BL/6J mice for 90 days. The energy intake and weight changes were measured every three days. After the dietary intervention, mice were sacrificed, liver and epididymal adipose tissues were taken for real-time polymerase chain reaction (RT-qPCR) analysis. Results The CGN in the high-fat diet restricted weight gain by decreasing liver and adipose mass without inhibiting energy intake.  The genes involving energy expenditure such as Acox1, Acadl, CPT-1A and Sirt1 were upregulated in the mice fed with carrageenan. However, the genes responsible for lipid synthesis were not significantly different compared to the diet-induced obese model. Conclusions The anti-obesity effect of the CGN in high-fat diet could be highly related to the enhancement of energy expenditure through up-regulating the downstream genes which promote β-oxidation by increasing the Sirt1 gene expression in liver. Funding Sources Ministry of Science and Technology of the People's Republic of China (10000 Talent Project)


Author(s):  
Sarah L McLennan ◽  
Amanda Henry ◽  
Lynne M Roberts ◽  
Sai S Siritharan ◽  
Melissa Ojurovic ◽  
...  

Abstract Background Preeclampsia is a major pregnancy complication associated with long-term maternal cardiometabolic disease. Research generally is focused on metabolic and pathophysiological changes during pregnancy, however, there is much less focus on the early postpartum period in subjects who suffered preeclampsia. The aim of this study was to (a) characterise energy intake and expenditure six months following normotensive and preeclamptic pregnancies, and (b) examine associations between energy balance, body composition, insulin resistance measures (HOMA-IR), and clinical characteristics. Design A cross-sectional study six months following normotensive (n=75) and preeclamptic (n=22) pregnancies was performed. Metabolic measurements included: anthropometrics measures, body composition via bioelectrical impedance analysis, 24-hour energy expenditure via SenseWear Armbands, energy intake via a three-day food diary, and serum metabolic parameters. Results Six months following preeclampsia, women had a significantly higher weight (77.3±20.9kg versus 64.5±11.4kg, p=0.01), fat mass percentage (FM%) (40.7±7.4% versus 34.9±8.1%, p=0.004), and insulin resistance (HOMA-IR 2.2±1.5 versus 1.0±0.7, p=0.003), as well as reduced HDL levels (1.5±0.4 mmol/L versus 1.8±0.4 mmol/L, p=0.01) compared to normotensive women. Women post-preeclampsia had lower activity-related energy expenditure (p=0.02) but a decreased total energy intake (p=0.02), leading to a more negative energy balance compared to their normotensive counterparts (-1,942 kJ/24-hours versus -480 kJ/24-hours; p=0.02). Conclusion Increases in insulin resistance and FM%, reduced HDL, and more sedentary lifestyles characterise the postpartum period following preeclamptic compared with normotensive pregnancies. Early post-preeclampsia interventions, such as lifestyle behaviour change, should be implemented and assessed to determine whether they reduce long-term cardiometabolic risk in women who experienced preeclampsia during pregnancy.


Endocrinology ◽  
2020 ◽  
Vol 162 (1) ◽  
Author(s):  
Hailan Liu ◽  
Chunmei Wang ◽  
Meng Yu ◽  
Yongjie Yang ◽  
Yang He ◽  
...  

Abstract AbstractCentral 5-hydroxytryptamine (5-HT), which is primarily synthesized by tryptophan hydroxylase 2 (TPH2) in the dorsal Raphe nuclei (DRN), plays a pivotal role in the regulation of food intake and body weight. However, the physiological functions of TPH2 on energy balance have not been consistently demonstrated. Here we systematically investigated the effects of TPH2 on energy homeostasis in adult male and female mice. We found that the DRN harbors a similar amount of TPH2+ cells in control male and female mice. Adult-onset TPH2 deletion in the DRN promotes hyperphagia and body weight gain only in male mice, but not in female mice. Ablation of TPH2 reduces hypothalamic pro-opiomelanocortin (POMC) neuronal activity robustly in males, but only to a modest degree in females. Deprivation of estrogen by ovariectomy (OVX) causes comparable food intake and weight gain in female control and DRN-specific TPH2 knockout mice. Nevertheless, disruption of TPH2 blunts the anorexigenic effects of exogenous estradiol (E2) and abolishes E2-induced activation of POMC neurons in OVX female mice, indicating that TPH2 is indispensable for E2 to activate POMC neurons and to suppress appetite. Together, our study revealed that TPH2 in the DRN contributes to energy balance regulation in a sexually dimorphic manner.


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