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Sequential Exposure to Obesogenic Factors in Females Rats: From Physiological Changes to Lipid Metabolism in Liver and Mesenteric Adipose Tissue

View Article: PubMed Central - PubMed

ABSTRACT

During their lifetime, females are subjected to different nutritional and hormonal factors that could increase the risk of obesity and associated comorbidities. From early postnatal periods until the postmenopausal phase, exposure to over nutrition, high-energy diet and oestrogen deficiency, are considered as significant obesity risk factors in women. In this study, we assessed how key transitional life events and exposure to different nutrition influence energy homeostasis in a rat model. Specifically, we assessed the sequential exposure to postnatal over nutrition, high-fat diet (HFD) after weaning, followed later by ovariectomy (OVX; as a model of menopause). Each obesity risk factor increased significantly body weight (BW) and adiposity, with additive effects after sequential exposure. Increased energy intake in both HFD and/or OVX groups, and decreased locomotor activity and energy expenditure after OVX can explain these metabolic changes. Our study also documents decreased lipogenic pathway in mesenteric adipose tissue after HFD and/or OVX, independent of previous postnatal programming, yet only HFD evoked this effect in liver. In addition, we report an increase in the expression of the hepatic PEPCK depending on previous metabolic status. Overall, our results identify the impact of different risk factors, which will help in understanding the development of obesity in females.

No MeSH data available.


Related in: MedlinePlus

Postnatal over feeding, high-fat diet and ovariectomy all increase body weight.(a) Body weight from day 5 until weaning in NL (normal litter) and SL (small litter) animals. (b) Body weight at weaning (PND24) (n = 105–10/group). (c) Body weight until ovariectomy. (d) Body weight at PND90, before ovariectomy (n = 50–55/group). (e) Body weight during sequential exposure to all risk factors. (f) Body weight at PND120 (n = 16–20/group). (g) Body weight gain after ovariectomy. (h) Body weight distribution of NL animals at PND120. (i) Body weight distribution of SL animals at PND120. (j) Percentage of obese animals at PND120 (body weights ranging between the average ± 3 standard deviations of the control group (NL-LFD-SHAM)). Annotation indicates significant effect of a = postnatal over feeding, b = HFD, c = OVX, d = significant HFD-OVX interaction (ANOVA) and ***p < 0.001 (t-test). All data are expressed as mean ± SEM.
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f1: Postnatal over feeding, high-fat diet and ovariectomy all increase body weight.(a) Body weight from day 5 until weaning in NL (normal litter) and SL (small litter) animals. (b) Body weight at weaning (PND24) (n = 105–10/group). (c) Body weight until ovariectomy. (d) Body weight at PND90, before ovariectomy (n = 50–55/group). (e) Body weight during sequential exposure to all risk factors. (f) Body weight at PND120 (n = 16–20/group). (g) Body weight gain after ovariectomy. (h) Body weight distribution of NL animals at PND120. (i) Body weight distribution of SL animals at PND120. (j) Percentage of obese animals at PND120 (body weights ranging between the average ± 3 standard deviations of the control group (NL-LFD-SHAM)). Annotation indicates significant effect of a = postnatal over feeding, b = HFD, c = OVX, d = significant HFD-OVX interaction (ANOVA) and ***p < 0.001 (t-test). All data are expressed as mean ± SEM.

Mentions: Our first goal was to study body weight accumulation from birth until weaning at postnatal day 24 (PND24). Animals were weighed from day 5, when a significantly higher weight was recorded in the small litter (SL) group because of postnatal over nutrition (Fig. 1a), and this difference increased through the lactation period (Fig. 1b). Once weaned, the animals were divided into two groups and fed diets with different fat content. Soon after, HFD-fed animals exhibited a higher body weight, and this effect was even greater in those animals that had previously been exposed to postnatal over nutrition (Fig. 1c and d). Thereafter, at postnatal day 90 (PND90) animals were ovariectomised in order to induce oestrogen deficiency. This sequential exposure allowed us to assess the individual influence of each obesogenic risk factor, and to uncover any interactions (Fig. 1e). So, although at postnatal day 120 (PND120), we found that each risk factor studied had a statistically significant effect on final body weight, the cumulative effect as unequal between groups. We found a statistically significant interaction between HFD and OVX. This reflected the fact that oestrogen deficiency did not have such a strong effect on the body weight of animals that had already been subjected to HFD (these animals showed a higher body weight already when they were ovariectomised; Fig. 1f). If observations were limited to the oestrogen-deficient period (Fig. 1g), ovariectomy elicited a significant body weight increase in all groups. The relevance of these changes in body weight was further assessed by assessing the number of animals that showed a marked increment in body weight; namely those with body weights ranging between the average ± 3 standard deviations of the control group (Normal Litter [NL]-Low fat diet [LFD]-Sham-operated [SHAM])28. Using this approach, we found a similar percentage of obese individuals following exposure to either HFD or OVX. Notably, sequential exposure to the three obesogenic stimuli led to marked body weight gain (up to 78% of animals are considered obese) (Fig. 1h–j).


Sequential Exposure to Obesogenic Factors in Females Rats: From Physiological Changes to Lipid Metabolism in Liver and Mesenteric Adipose Tissue
Postnatal over feeding, high-fat diet and ovariectomy all increase body weight.(a) Body weight from day 5 until weaning in NL (normal litter) and SL (small litter) animals. (b) Body weight at weaning (PND24) (n = 105–10/group). (c) Body weight until ovariectomy. (d) Body weight at PND90, before ovariectomy (n = 50–55/group). (e) Body weight during sequential exposure to all risk factors. (f) Body weight at PND120 (n = 16–20/group). (g) Body weight gain after ovariectomy. (h) Body weight distribution of NL animals at PND120. (i) Body weight distribution of SL animals at PND120. (j) Percentage of obese animals at PND120 (body weights ranging between the average ± 3 standard deviations of the control group (NL-LFD-SHAM)). Annotation indicates significant effect of a = postnatal over feeding, b = HFD, c = OVX, d = significant HFD-OVX interaction (ANOVA) and ***p < 0.001 (t-test). All data are expressed as mean ± SEM.
© Copyright Policy - open-access
Related In: Results  -  Collection

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f1: Postnatal over feeding, high-fat diet and ovariectomy all increase body weight.(a) Body weight from day 5 until weaning in NL (normal litter) and SL (small litter) animals. (b) Body weight at weaning (PND24) (n = 105–10/group). (c) Body weight until ovariectomy. (d) Body weight at PND90, before ovariectomy (n = 50–55/group). (e) Body weight during sequential exposure to all risk factors. (f) Body weight at PND120 (n = 16–20/group). (g) Body weight gain after ovariectomy. (h) Body weight distribution of NL animals at PND120. (i) Body weight distribution of SL animals at PND120. (j) Percentage of obese animals at PND120 (body weights ranging between the average ± 3 standard deviations of the control group (NL-LFD-SHAM)). Annotation indicates significant effect of a = postnatal over feeding, b = HFD, c = OVX, d = significant HFD-OVX interaction (ANOVA) and ***p < 0.001 (t-test). All data are expressed as mean ± SEM.
Mentions: Our first goal was to study body weight accumulation from birth until weaning at postnatal day 24 (PND24). Animals were weighed from day 5, when a significantly higher weight was recorded in the small litter (SL) group because of postnatal over nutrition (Fig. 1a), and this difference increased through the lactation period (Fig. 1b). Once weaned, the animals were divided into two groups and fed diets with different fat content. Soon after, HFD-fed animals exhibited a higher body weight, and this effect was even greater in those animals that had previously been exposed to postnatal over nutrition (Fig. 1c and d). Thereafter, at postnatal day 90 (PND90) animals were ovariectomised in order to induce oestrogen deficiency. This sequential exposure allowed us to assess the individual influence of each obesogenic risk factor, and to uncover any interactions (Fig. 1e). So, although at postnatal day 120 (PND120), we found that each risk factor studied had a statistically significant effect on final body weight, the cumulative effect as unequal between groups. We found a statistically significant interaction between HFD and OVX. This reflected the fact that oestrogen deficiency did not have such a strong effect on the body weight of animals that had already been subjected to HFD (these animals showed a higher body weight already when they were ovariectomised; Fig. 1f). If observations were limited to the oestrogen-deficient period (Fig. 1g), ovariectomy elicited a significant body weight increase in all groups. The relevance of these changes in body weight was further assessed by assessing the number of animals that showed a marked increment in body weight; namely those with body weights ranging between the average ± 3 standard deviations of the control group (Normal Litter [NL]-Low fat diet [LFD]-Sham-operated [SHAM])28. Using this approach, we found a similar percentage of obese individuals following exposure to either HFD or OVX. Notably, sequential exposure to the three obesogenic stimuli led to marked body weight gain (up to 78% of animals are considered obese) (Fig. 1h–j).

View Article: PubMed Central - PubMed

ABSTRACT

During their lifetime, females are subjected to different nutritional and hormonal factors that could increase the risk of obesity and associated comorbidities. From early postnatal periods until the postmenopausal phase, exposure to over nutrition, high-energy diet and oestrogen deficiency, are considered as significant obesity risk factors in women. In this study, we assessed how key transitional life events and exposure to different nutrition influence energy homeostasis in a rat model. Specifically, we assessed the sequential exposure to postnatal over nutrition, high-fat diet (HFD) after weaning, followed later by ovariectomy (OVX; as a model of menopause). Each obesity risk factor increased significantly body weight (BW) and adiposity, with additive effects after sequential exposure. Increased energy intake in both HFD and/or OVX groups, and decreased locomotor activity and energy expenditure after OVX can explain these metabolic changes. Our study also documents decreased lipogenic pathway in mesenteric adipose tissue after HFD and/or OVX, independent of previous postnatal programming, yet only HFD evoked this effect in liver. In addition, we report an increase in the expression of the hepatic PEPCK depending on previous metabolic status. Overall, our results identify the impact of different risk factors, which will help in understanding the development of obesity in females.

No MeSH data available.


Related in: MedlinePlus