scholarly journals Testosterone reduces body fat in male mice by stimulation of physical activity via extrahypothalamic ERα signaling

Author(s):  
Na Ri Kim ◽  
Karel David ◽  
Katrien Corbeels ◽  
Rougin Khalil ◽  
Leen Antonio ◽  
...  

Abstract Testosterone (T) reduces male fat mass but the underlying mechanisms remain elusive, limiting its clinical relevance in hypogonadism-associated obesity. Here, we subjected chemically castrated high fat diet-induced adult obese male mice to supplementation with T or the non-aromatizable androgen dihydrotestosterone (DHT) for 20 weeks. Both hormones increased lean mass, thereby indirectly increasing oxygen consumption and energy expenditure. In addition, T but not DHT decreased fat mass and increased ambulatory activity, indicating a role for aromatization into estrogens. Investigation of the pattern of aromatase expression in various murine tissues revealed absence of Cyp19a1 expression in adipose tissue while high levels were observed in brain and gonads. In obese hypogonadal male mice with extrahypothalamic neuronal estrogen receptor alpha deletion (N-ERαKO), T still increased lean mass but was unable to decrease fat mass. Stimulatory effect of T on ambulatory activity was also abolished in N-ERαKO males. In conclusion, our work demonstrates that the fat-burning action of T is dependent on aromatization into estrogens and is at least partially mediated by stimulation of physical activity via extrahypothalamic ERα signaling. In contrast, the increase in lean mass upon T supplementation is mediated through the androgen receptor and indirectly leads to an increase in energy expenditure, which might also contribute to the fat-burning effects of T.

2007 ◽  
Vol 39 (Supplement) ◽  
pp. S439
Author(s):  
Gunnhildur Hinriksdóttir ◽  
Sigurbjörn Á. Arngrímsson ◽  
Mark M. Misic ◽  
Daina M. Mallard ◽  
Ellen M. Evans

Author(s):  
Nils Abel Aars ◽  
Bjarne K. Jacobsen ◽  
Bente Morseth ◽  
Nina Emaus ◽  
Sameline Grimsgaard

Abstract Background It is not clear how physical activity affects body composition in adolescents. Physical activity levels are often reduced during this period, and the relative proportion of body fat mass and lean mass undergo natural changes in growing adolescents. We aimed to examine whether self-reported physical activity in leisure time at baseline or change in activity during follow-up affect changes in four measures of body composition; body mass index (kg/m2), waist circumference, fat mass index (fat mass in kg/m2) and lean mass index (lean mass in kg/m2). Methods We used data from the Tromsø Study Fit Futures, which invited all first year students in upper secondary high school in two municipalities in northern Norway in 2010–2011. They were reexamined in 2012–2013. Longitudinal data was available for 292 boys and 354 girls. We used multiple linear regression analyses to assess whether self-reported level of physical activity in leisure time at baseline predicted changes in body composition, and analysis of covariance to assess the effects of change in level of activity during follow-up on change in body composition. All analyses were performed sex-specific, and a p-value of < 0.05 was considered statistically significant. Results There were no associations between self-reported leisure time physical activity in the first year of upper secondary high school and changes in any of the considered measure of body composition after 2 years of follow up, with the exception of waist circumference in boys (p = 0.05). In boys, change in fat mass index differed significantly between groups of activity change (p < 0.01), with boys adopting activity or remaining physically active having less increase in fat mass index than the consistently inactive. In girls, change in lean mass index differed significantly between groups of activity change (p = 0.04), with girls adopting physical activity having the highest increase. Conclusions Self-reported leisure time physical activity does not predict changes in body composition in adolescents after 2 years of follow up. Change in the level of physical activity is associated with change in fat mass index in boys and lean mass index in girls.


2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
María Pardo ◽  
Ana B. Crujeiras ◽  
María Amil ◽  
Zaida Aguera ◽  
Susana Jiménez-Murcia ◽  
...  

FNDC5/irisin has been recently postulated as beneficial in the treatment of obesity and diabetes because it is induced in muscle by exercise, increasing energy expenditure. However, recent reports have shown that WAT also secretes irisin and that circulating irisin is elevated in obese subjects. The aim of this study was to evaluate irisin levels in conditions of extreme BMI and its correlation with basal metabolism and daily activity. The study involved 145 female patients, including 96 with extreme BMIs (30 anorexic (AN) and 66 obese (OB)) and 49 healthy normal weight (NW). The plasma irisin levels were significantly elevated in the OB patients compared with the AN and NW patients. Irisin also correlated positively with body weight, BMI, and fat mass. The OB patients exhibited the highest REE and higher daily physical activity compared with the AN patients but lower activity compared with the NW patients. The irisin levels were inversely correlated with daily physical activity and directly correlated with REE. Fat mass contributed to most of the variability of the irisin plasma levels independently of the other studied parameters.Conclusion. Irisin levels are influenced by energy expenditure independently of daily physical activity but fat mass is the main contributing factor.


2017 ◽  
Vol 26 (5) ◽  
pp. 461-466 ◽  
Author(s):  
Jing Xiang ◽  
Yongjie Chen ◽  
Yupeng Wang ◽  
Shaofei Su ◽  
Xinyu Wang ◽  
...  

2011 ◽  
Vol 301 (5) ◽  
pp. E767-E778 ◽  
Author(s):  
Kesha Rana ◽  
Barbara C. Fam ◽  
Michele V. Clarke ◽  
Tammy P. S. Pang ◽  
Jeffrey D. Zajac ◽  
...  

In men, as testosterone levels decrease, fat mass increases and muscle mass decreases. Increased fat mass in men, in particular central obesity, is a major risk factor for type 2 diabetes, cardiovascular disease, and all-cause mortality. Testosterone treatment has been shown to decrease fat mass and increase fat-free mass. We hypothesize that androgens act directly via the DNA binding-dependent actions of the androgen receptor (AR) to regulate genes controlling fat mass and metabolism. The aim of this study was to determine the effect of a global DNA binding-dependent (DBD) AR knockout (DBD-ARKO) on the metabolic phenotype in male mice by measuring body mass, fat mass, food intake, voluntary physical activity, resting energy expenditure, substrate oxidation rates, serum glucose, insulin, lipid, and hormone levels, and metabolic gene expression levels and second messenger protein levels. DBD-ARKO males have increased adiposity despite a decreased total body mass compared with wild-type (WT) males. DBD-ARKO males showed reduced voluntary activity, decreased food intake, increased serum leptin and adiponectin levels, an altered lipid metabolism gene profile, and increased phosphorylated CREB levels compared with WT males. This study demonstrates that androgens acting via the DNA binding-dependent actions of the AR regulate fat mass and metabolism in males and that the increased adiposity in DBD-ARKO male mice is associated with decreased voluntary activity, hyperleptinemia and hyperadiponectinemia and not with insulin resistance, increased food intake, or decreased resting energy expenditure.


2015 ◽  
Vol 75 (1) ◽  
pp. 73-77 ◽  
Author(s):  
Shaoyu Zhu ◽  
Jesse Eclarinal ◽  
Maria S. Baker ◽  
Ge Li ◽  
Robert A. Waterland

Extensive human and animal model data show that environmental influences during critical periods of prenatal and early postnatal development can cause persistent alterations in energy balance regulation. Although a potentially important factor in the worldwide obesity epidemic, the fundamental mechanisms underlying such developmental programming of energy balance are poorly understood, limiting our ability to intervene. Most studies of developmental programming of energy balance have focused on persistent alterations in the regulation of energy intake; energy expenditure has been relatively underemphasised. In particular, very few studies have evaluated developmental programming of physical activity. The aim of this review is to summarise recent evidence that early environment may have a profound impact on establishment of individual propensity for physical activity. Recently, we characterised two different mouse models of developmental programming of obesity; one models fetal growth restriction followed by catch-up growth, and the other models early postnatal overnutrition. In both studies, we observed alterations in body-weight regulation that persisted to adulthood, but no group differences in food intake. Rather, in both cases, programming of energy balance appeared to be due to persistent alterations in energy expenditure and spontaneous physical activity (SPA). These effects were stronger in female offspring. We are currently exploring the hypothesis that developmental programming of SPA occurs via induced sex-specific alterations in epigenetic regulation in the hypothalamus and other regions of the central nervous system. We will summarise the current progress towards testing this hypothesis. Early environmental influences on establishment of physical activity are likely an important factor in developmental programming of energy balance. Understanding the fundamental underlying mechanisms in appropriate animal models will help determine whether early life interventions may be a practical approach to promote physical activity in man.


2003 ◽  
Vol 90 (6) ◽  
pp. 1133-1139 ◽  
Author(s):  
Elaine C. Rush ◽  
Lindsay D. Plank ◽  
Peter S. W. Davies ◽  
Patsy Watson ◽  
Clare R. Wall

Body fatness and the components of energy expenditure in children aged 5–14 years were investigated. In a group of seventy-nine healthy children (thirty-nine female, forty male), mean age 10·0 (sd 2·8) years, comprising twenty-seven Maori, twenty-six Pacific Island and twenty-six European, total energy expenditure (TEE) was determined over 10 d using the doubly-labelled water method. Resting metabolic rate (RMR) was measured by indirect calorimetry and physical activity level (PAL) was calculated as TEE:RMR. Fat-free mass (FFM), and hence fat mass, was derived from the 18O-dilution space using appropriate values for FFM hydration in children. Qualitative information on physical activity patterns was obtained by questionnaire. Maori and Pacific children had a higher BMI than European children (P<0·003), but % body fat was similar for the three ethnic groups. The % body fat increased with age for girls (r 0·42, P=0·008), but not for boys. Ethnicity was not a significant predictor of RMR adjusted for FFM and fat mass. TEE and PAL, adjusted for body weight and age, were higher in Maori than European children (P<0·02), with Pacific children having intermediate values. PAL was inversely correlated with % body fat in boys (r −0·43, P=0·006), but was not significantly associated in girls. The % body fat was not correlated with reported time spent inactive or outdoors. Ethnic-related differences in total and activity-related energy expenditure that might account for higher obesity rates in Maori and Pacific children were not seen. Low levels of physical activity were associated with increased body fat in boys but not in girls.


Endocrinology ◽  
2018 ◽  
Vol 159 (7) ◽  
pp. 2676-2682 ◽  
Author(s):  
Claes Ohlsson ◽  
Daniel A Hägg ◽  
Fredrik Hammarhjelm ◽  
Adrià Dalmau Gasull ◽  
Jakob Bellman ◽  
...  
Keyword(s):  
Fat Mass ◽  

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 526-526
Author(s):  
Rachel Silver ◽  
Sai Das ◽  
Michael Lowe ◽  
Susan Roberts

Abstract Objectives There is persistent controversy over the extent to which different components of energy expenditure disproportionately decrease after weight loss and contribute to weight regain through decreased energy requirements. We conducted a secondary analysis of the CALERIE I study to test the hypothesis that decreased resting metabolic rate (RMR) and energy expenditure for physical activity (EEPA) after a 6-month calorie restriction intervention would predict weight regain at 12 months, with a greater decrease in RMR than EEPA. Methods Participants (n = 46) received all food and energy-containing beverages for 6 months. Outcome measures included total energy expenditure by doubly labeled water, RMR by indirect calorimetry, and body composition by BOD POD. Predictions for RMR and EEPA were derived from baseline linear regression models including age, sex, fat mass, and fat free mass. Baseline regression coefficients were used to calculate the predicted RMR and EEPA at 6 months. Residuals were calculated as the difference between measured and predicted values and were adjusted for body weight. The presence of metabolic adaptation was evaluated by a paired t-test comparing measured and predicted RMR at 6 months. Differences between 6-month RMR and EEPA residuals were evaluated by the same method. Linear regression was used to assess the association between 6-month residuals and weight loss maintenance (% weight change, 6 to 12 months). Results Mean weight loss was 6.9% at 6 months with 2.1% regain from 6 to 12 months. No adaptation in RMR was observed at 6 months (mean residual: 19 kcal; 95% confidence interval: −9, 48; P = 0.18). However, significant adaptation was observed in EEPA (mean residual: −199 kcal; −126, −272; P &lt; 0.0001). In addition, the mean 6-month RMR residual was significantly greater than the mean 6-month EEPA residual (218 kcal; 133, 304; P &lt; 0.0001). There was no significant association between 6-month RMR or EEPA residuals and weight regain at 12 months (P = 0.56, 0.34). Conclusions There was no measurable decrease in RMR with weight loss after adjusting for changes in fat free mass and fat mass, but there was a decrease in EEPA. Changes in RMR and EEPA with weight loss over 6 months did not predict weight regain at 12 months. Funding Sources Jean Mayer USDA Human Nutrition Research Center on Aging Doctoral Scholarship; USDA agreement #8050–51000-105–01S


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