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Intestinal mucosal triacylglycerol accumulation secondary to decreased lipid secretion in obese and high fat fed mice.

Douglass JD, Malik N, Chon SH, Wells K, Zhou YX, Choi AS, Joseph LB, Storch J - Front Physiol (2012)

Bottom Line: Fewer changes were found in mucosal samples from the fasted state animals.Remarkably, oral fat tolerance tests showed a striking reduction in the plasma appearance of an oral fat load in the ob/ob and WT-HF mice compared to WT-LF.Moreover, even in the absence of frank obesity, HF feeding leads to a large decrease in the rate of intestinal lipid secretion.

View Article: PubMed Central - PubMed

Affiliation: Department of Nutritional Sciences, School of Environmental and Biological Sciences, Rutgers University New Brunswick, NJ, USA.

ABSTRACT
The ectopic deposition of fat in liver and muscle during obesity is well established, however surprisingly little is known about the intestine. We used the ob/ob mouse and C57BL6/J mice fed a high fat (HF) diet to examine the effects of obesity and the effects of HF feeding, respectively, on intestinal mucosal triacylglycerol (TG) accumulation. Male C57BL6/J (wild-type, WT) mice were fed low fat (LF; 10% kcal as fat) or HF (45%) diets, and ob/ob mice were fed the LF diet, for 3 weeks. In this time frame, the WT-HF mice did not become obese, enabling independent examination of effects of the HF diet and effects of obesity. Analysis of intestinal lipid extracts from fed and fasted animals demonstrated that the mucosa, like other tissues, accumulates excess lipid. In the fed state, mucosal triacylglycerol (TG) levels were threefold and fivefold higher in the WT-HF and ob/ob mice, respectively, relative to the WT-LF mice. In the fasted state, mucosa from ob/ob mice had threefold higher TG levels relative to WT-LF mucosa. q-PCR analysis of mucosal mRNA from fed state mice showed alterations in the expression of several genes related to both anabolic and catabolic lipid metabolism pathways in WT-HF and ob/ob mice relative to WT-LF controls. Fewer changes were found in mucosal samples from the fasted state animals. Remarkably, oral fat tolerance tests showed a striking reduction in the plasma appearance of an oral fat load in the ob/ob and WT-HF mice compared to WT-LF. Overall, the results demonstrate that the intestinal mucosa accumulates excess TG during obesity. Changes in the expression of lipid metabolic and transport genes, as well as reduced secretion of dietary lipid from the mucosal cells into the circulation, may contribute to the TG accumulation in intestinal mucosa during obesity. Moreover, even in the absence of frank obesity, HF feeding leads to a large decrease in the rate of intestinal lipid secretion.

No MeSH data available.


Related in: MedlinePlus

Weight and body fat of mouse models. (A) Average body weight of mice over the 3-week feeding study. Error bars may not be visible within data point. (B) Percent body fat as determined by EchoMRI. (C) Percent of total body weight as epididymal fat determined by tissue weight. Data represent average ± SEM, p < 0.05 or lower versus WT–LF, n = 5–6 for WT, n = 3 for ob/ob.
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Figure 1: Weight and body fat of mouse models. (A) Average body weight of mice over the 3-week feeding study. Error bars may not be visible within data point. (B) Percent body fat as determined by EchoMRI. (C) Percent of total body weight as epididymal fat determined by tissue weight. Data represent average ± SEM, p < 0.05 or lower versus WT–LF, n = 5–6 for WT, n = 3 for ob/ob.

Mentions: As expected at baseline the WT mice had a substantially lower body weight than their age-matched ob/ob counterparts (Figure 1A). Following the 3-week feeding period, the ob/ob maintained their weight. The WT–LF and WT–HF groups gained approximately 3 g/mouse (Figure 1A). At the end of the 3-weeks, body composition was assessed by MRI and showed that the ob/ob mice had a significantly higher percentage of total body fat than both the WT–LF and WT–HF groups (Figure 1B). There was no significant difference in total body fat percentage between the WT–LF and WT–HF groups. The ob/ob group also displayed significantly more epididymal fat as a percentage of their body weight than either WT group (Figure 1C). While there was a trend of higher percent epididymal fat in the WT–HF compared to WT–LF mice, it did not reach statistical significance. The hedonic mouse strain C57BL6/J tends to develop obesity and hyperglycemia (Petro et al., 2004). That the WT–HF mice did not gain weight relative to the WT–LF group is in contrast to our previous studies using older mice (Chon et al., 2007), however, this allowed a comparison between the effects of HF feeding in the absence of obesity, to the effects of genetically mediated obesity.


Intestinal mucosal triacylglycerol accumulation secondary to decreased lipid secretion in obese and high fat fed mice.

Douglass JD, Malik N, Chon SH, Wells K, Zhou YX, Choi AS, Joseph LB, Storch J - Front Physiol (2012)

Weight and body fat of mouse models. (A) Average body weight of mice over the 3-week feeding study. Error bars may not be visible within data point. (B) Percent body fat as determined by EchoMRI. (C) Percent of total body weight as epididymal fat determined by tissue weight. Data represent average ± SEM, p < 0.05 or lower versus WT–LF, n = 5–6 for WT, n = 3 for ob/ob.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3285813&req=5

Figure 1: Weight and body fat of mouse models. (A) Average body weight of mice over the 3-week feeding study. Error bars may not be visible within data point. (B) Percent body fat as determined by EchoMRI. (C) Percent of total body weight as epididymal fat determined by tissue weight. Data represent average ± SEM, p < 0.05 or lower versus WT–LF, n = 5–6 for WT, n = 3 for ob/ob.
Mentions: As expected at baseline the WT mice had a substantially lower body weight than their age-matched ob/ob counterparts (Figure 1A). Following the 3-week feeding period, the ob/ob maintained their weight. The WT–LF and WT–HF groups gained approximately 3 g/mouse (Figure 1A). At the end of the 3-weeks, body composition was assessed by MRI and showed that the ob/ob mice had a significantly higher percentage of total body fat than both the WT–LF and WT–HF groups (Figure 1B). There was no significant difference in total body fat percentage between the WT–LF and WT–HF groups. The ob/ob group also displayed significantly more epididymal fat as a percentage of their body weight than either WT group (Figure 1C). While there was a trend of higher percent epididymal fat in the WT–HF compared to WT–LF mice, it did not reach statistical significance. The hedonic mouse strain C57BL6/J tends to develop obesity and hyperglycemia (Petro et al., 2004). That the WT–HF mice did not gain weight relative to the WT–LF group is in contrast to our previous studies using older mice (Chon et al., 2007), however, this allowed a comparison between the effects of HF feeding in the absence of obesity, to the effects of genetically mediated obesity.

Bottom Line: Fewer changes were found in mucosal samples from the fasted state animals.Remarkably, oral fat tolerance tests showed a striking reduction in the plasma appearance of an oral fat load in the ob/ob and WT-HF mice compared to WT-LF.Moreover, even in the absence of frank obesity, HF feeding leads to a large decrease in the rate of intestinal lipid secretion.

View Article: PubMed Central - PubMed

Affiliation: Department of Nutritional Sciences, School of Environmental and Biological Sciences, Rutgers University New Brunswick, NJ, USA.

ABSTRACT
The ectopic deposition of fat in liver and muscle during obesity is well established, however surprisingly little is known about the intestine. We used the ob/ob mouse and C57BL6/J mice fed a high fat (HF) diet to examine the effects of obesity and the effects of HF feeding, respectively, on intestinal mucosal triacylglycerol (TG) accumulation. Male C57BL6/J (wild-type, WT) mice were fed low fat (LF; 10% kcal as fat) or HF (45%) diets, and ob/ob mice were fed the LF diet, for 3 weeks. In this time frame, the WT-HF mice did not become obese, enabling independent examination of effects of the HF diet and effects of obesity. Analysis of intestinal lipid extracts from fed and fasted animals demonstrated that the mucosa, like other tissues, accumulates excess lipid. In the fed state, mucosal triacylglycerol (TG) levels were threefold and fivefold higher in the WT-HF and ob/ob mice, respectively, relative to the WT-LF mice. In the fasted state, mucosa from ob/ob mice had threefold higher TG levels relative to WT-LF mucosa. q-PCR analysis of mucosal mRNA from fed state mice showed alterations in the expression of several genes related to both anabolic and catabolic lipid metabolism pathways in WT-HF and ob/ob mice relative to WT-LF controls. Fewer changes were found in mucosal samples from the fasted state animals. Remarkably, oral fat tolerance tests showed a striking reduction in the plasma appearance of an oral fat load in the ob/ob and WT-HF mice compared to WT-LF. Overall, the results demonstrate that the intestinal mucosa accumulates excess TG during obesity. Changes in the expression of lipid metabolic and transport genes, as well as reduced secretion of dietary lipid from the mucosal cells into the circulation, may contribute to the TG accumulation in intestinal mucosa during obesity. Moreover, even in the absence of frank obesity, HF feeding leads to a large decrease in the rate of intestinal lipid secretion.

No MeSH data available.


Related in: MedlinePlus