Early life stress reduces voluntary exercise and its prevention of diet-induced obesity and metabolic dysfunction in mice.

AbstractThe development of obesity-related metabolic syndrome (MetS) involves a complex interaction of genetic and environmental factors. One environmental factor found to be significantly associated with MetS is early life stress (ELS). We have previously reported on our mouse model of ELS, induced by neonatal maternal separation (NMS), that displays altered regulation of the hypothalamic-pituitary-adrenal (HPA) axis and increased sensitivity in the urogenital organs, which was attenuated by voluntary wheel running. Here, we are using our NMS model to determine if ELS-induced changes in the HPA axis also influence weight gain and MetS. Naïve (non-stressed) and NMS male mice were given free access to a running wheel and a low-fat control diet at 4-weeks of age. At 16-weeks of age, half of the mice were transitioned to a high fat/sucrose (HFS) diet to investigate if NMS influences the effectiveness of voluntary exercise to prevent diet-induced obesity and MetS. Overall, we observed a greater impact of voluntary exercise on prevention of HFS diet-induced outcomes in naïve mice, compared to NMS mice. Although body weight and fat mass were still significantly higher, exercise attenuated fasting insulin levels and mRNA levels of inflammatory markers in epididymal adipose tissue in HFS diet-fed naïve mice. Only moderate changes were observed in exercised NMS mice on a HFS diet, although this could partially be explained by reduced running distance within this group. Interestingly, sedentary NMS mice on a control diet displayed impaired glucose homeostasis and moderately increased pro-inflammatory mRNA levels in epididymal adipose, suggesting that early life stress alone impairs metabolic function and negatively impacts the therapeutic effect of voluntary exercise.

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(267) The Influence of Long-Term Western Diet and Voluntary Exercise in an Early Life Stress Mouse Model of Co-Morbid Disorders

Journal of Pain ◽

10.1016/j.jpain.2019.01.189 ◽

2019 ◽

Vol 20 (4) ◽

pp. S41

Author(s):

O. Eller-Smith ◽

X. Yang ◽

E. Morris ◽

J. Thyfault ◽

J. Christianson

Keyword(s):

Mouse Model ◽

Life Stress ◽

Early Life ◽

Early Life Stress ◽

Western Diet ◽

Voluntary Exercise

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P5.2 The effect of voluntary exercise and high fat diet on tyrosine hydroxylase phosphorylation in male Sprague–Dawley rats exposed to early life stress

Autonomic Neuroscience ◽

10.1016/j.autneu.2009.05.192 ◽

2009 ◽

Vol 149 (1-2) ◽

pp. 103

Author(s):

L.K. Ong ◽

J. Maniam ◽

P.R. Dunkley ◽

L. Bobrovskaya ◽

M.J. Morris

Keyword(s):

Tyrosine Hydroxylase ◽

High Fat Diet ◽

Life Stress ◽

Early Life ◽

Early Life Stress ◽

Voluntary Exercise ◽

Sprague Dawley ◽

High Fat ◽

Sprague Dawley Rats ◽

Tyrosine Hydroxylase Phosphorylation

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Postnatal treatment with metyrapone attenuates the effects of diet-induced obesity in female rats exposed to early-life stress

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00308.2016 ◽

2017 ◽

Vol 312 (2) ◽

pp. E98-E108 ◽

Cited By ~ 13

Author(s):

Margaret O. Murphy ◽

Joseph B. Herald ◽

Caleb T. Wills ◽

Stanley G. Unfried ◽

Dianne M. Cohn ◽

...

Keyword(s):

Metabolic Disease ◽

Glucose Intolerance ◽

Life Stress ◽

Early Life ◽

Early Life Stress ◽

Female Rats ◽

Male Rats ◽

Female Rat ◽

Diet Induced Obesity ◽

Postnatal Treatment

Experimental studies in rodents have shown that females are more susceptible to exhibiting fat expansion and metabolic disease compared with males in several models of fetal programming. This study tested the hypothesis that female rat pups exposed to maternal separation (MatSep), a model of early-life stress, display an exacerbated response to diet-induced obesity compared with male rats. Also, we tested whether the postnatal treatment with metyrapone (MTP), a corticosterone synthase inhibitor, would attenuate this phenotype. MatSep was performed in WKY offspring by separation from the dam (3 h/day, postnatal days 2–14). Upon weaning, male and female rats were placed on a normal (ND; 18% kcal fat) or high-fat diet (HFD; 60% kcal fat). Nondisturbed littermates served as controls. In male rats, no diet-induced differences in body weight (BW), glucose tolerance, and fat tissue weight and morphology were found between MatSep and control male rats. However, female MatSep rats displayed increased BW gain, fat pad weights, and glucose intolerance compared with control rats ( P < 0.05). Also, HFD increased plasma corticosterone (196 ± 51 vs. 79 ± 18 pg/ml, P < 0.05) and leptin levels (1.8 ± 0.4 vs. 1.3 ± 0.1 ng/ml, P < 0.05) in female MatSep compared with control rats, whereas insulin and adiponectin levels were similar between groups. Female control and MatSep offspring were treated with MTP (50 µg/g ip) 30 min before the daily separation. MTP treatment significantly attenuated diet-induced obesity risk factors, including elevated adiposity, hyperleptinemia, and glucose intolerance. These findings show that exposure to stress hormones during early life could be a key event to enhance diet-induced obesity and metabolic disease in female rats. Thus, pharmacological and/or behavioral inflection of the stress levels is a potential therapeutic approach for prevention of early life stress-enhanced obesity and metabolic disease.

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