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The intrauterine and nursing period is a window of susceptibility for development of obesity and intestinal tumorigenesis by a high fat diet in Min/+ mice as adults.

Ngo HT, Hetland RB, Steffensen IL - J Obes (2015)

Bottom Line: We studied how obesogenic conditions during various life periods affected obesity and intestinal tumorigenesis in adult C57BL/6J-Min (multiple intestinal neoplasia)/+ mice.In the glucose tolerance test, the early exposure to a 45% fat diet in utero, during nursing, or during both in utero and nursing, did not affect blood glucose, whereas a 45% fat diet given to adults or throughout life did.The intrauterine and nursing period is a window of susceptibility for dietary fat-induced obesity and intestinal tumor development.

View Article: PubMed Central - PubMed

Affiliation: Department of Food, Water and Cosmetics, Division of Environmental Medicine, Norwegian Institute of Public Health, P.O. Box 4404 Nydalen, 0403 Oslo, Norway.

ABSTRACT
We studied how obesogenic conditions during various life periods affected obesity and intestinal tumorigenesis in adult C57BL/6J-Min (multiple intestinal neoplasia)/+ mice. The mice were given a 10% fat diet throughout life (negative control) or a 45% fat diet in utero, during nursing, during both in utero and nursing, during adult life, or during their whole life-span, and terminated at 11 weeks for tumorigenesis (Min/+) or 23 weeks for obesogenic effect (wild-type). Body weight at 11 weeks was increased after a 45% fat diet during nursing, during both in utero and nursing, and throughout life, but had normalized at 23 weeks. In the glucose tolerance test, the early exposure to a 45% fat diet in utero, during nursing, or during both in utero and nursing, did not affect blood glucose, whereas a 45% fat diet given to adults or throughout life did. However, a 45% fat diet during nursing or during in utero and nursing increased the number of small intestinal tumors. So did exposures to a 45% fat diet in adult life or throughout life, but without increasing the tumor numbers further. The intrauterine and nursing period is a window of susceptibility for dietary fat-induced obesity and intestinal tumor development.

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Related in: MedlinePlus

Experimental design. The mice were exposed to a 45% fat diet for combinations of three periods in life; (1) in utero, via the dams, (2) from birth to weaning, via milk during nursing, or (3) from weaning at 3 weeks to termination at 11 weeks of age (for Min/+ mice) or 23 weeks (for wild-type mice), to determine the most susceptible exposure period for development of obesity and intestinal tumorigenesis as adults. The effects of a 45% fat diet were studied on spontaneous tumorigenesis induced by the inherited mutation in the Apc gene and on tumors induced by the the food mutagen and carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). The mice in two experimental groups (marked with arrows) were given one s.c. injection of 25 mg/kg body weight of PhIP on days 3–6 after birth. In total, eight experimental groups were included in this experiment; a 10% fat diet throughout life as a negative control (10+10+10), a 45% fat diet in utero (45+10+10), a 45% fat diet during the nursing period (10+45+10), a 45% fat diet both in utero and during nursing (45+45+10), exposed to PhIP or not, a 45% fat diet as adults (10+10+45), or a 45% fat diet throughout life (45+45+45), exposed to PhIP or not.
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fig1: Experimental design. The mice were exposed to a 45% fat diet for combinations of three periods in life; (1) in utero, via the dams, (2) from birth to weaning, via milk during nursing, or (3) from weaning at 3 weeks to termination at 11 weeks of age (for Min/+ mice) or 23 weeks (for wild-type mice), to determine the most susceptible exposure period for development of obesity and intestinal tumorigenesis as adults. The effects of a 45% fat diet were studied on spontaneous tumorigenesis induced by the inherited mutation in the Apc gene and on tumors induced by the the food mutagen and carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). The mice in two experimental groups (marked with arrows) were given one s.c. injection of 25 mg/kg body weight of PhIP on days 3–6 after birth. In total, eight experimental groups were included in this experiment; a 10% fat diet throughout life as a negative control (10+10+10), a 45% fat diet in utero (45+10+10), a 45% fat diet during the nursing period (10+45+10), a 45% fat diet both in utero and during nursing (45+45+10), exposed to PhIP or not, a 45% fat diet as adults (10+10+45), or a 45% fat diet throughout life (45+45+45), exposed to PhIP or not.

Mentions: Diets of purified ingredients from Research Diets Inc. (New Brunswick, NJ, USA) were used. The D12451 diet, containing 20%, 35%, and 45% of kcal from protein, carbohydrates, and fat, respectively, was used as a high fat diet. The D12450H diet, containing 20%, 70%, and 10% of kcal from protein, carbohydrates, and fat, respectively, was used as a matching control low fat diet. The amount of sucrose was 17% of the calories in both diets. The high fat diet had 4.73 kcal/g, whereas the low fat diet had 3.85 kcal/g; that is, the high fat diet contained 22.9% more kcal per gram diet. In order to avoid that the dietary treatment was unevenly spread out in time, we gave the first dam 10% fat diet, the second dam 45% fat diet, the third dam 10% fat diet, the forth dam 45% fat diet, and so on. Similarly, the litters of offspring were given either of the two diets after birth every other time and after weaning every other time until the necessary numbers in all experimental dietary groups were obtained (Figure 1). The number of litters (given in parentheses) in each treatment group was 10% fat diet throughout life (17), 45% fat diet in utero (17), 45% fat diet during the nursing period (14), 45% fat diet in utero and during the nursing period (19), 45% fat diet as adults (18), and 45% fat diet throughout life (21). For the groups also given PhIP, the number of litters was 45% fat diet in utero and during the nursing period (17) and 45% fat diet throughout life (17). The number of mice in each treatment group is given in the figures and tables for the various end points.


The intrauterine and nursing period is a window of susceptibility for development of obesity and intestinal tumorigenesis by a high fat diet in Min/+ mice as adults.

Ngo HT, Hetland RB, Steffensen IL - J Obes (2015)

Experimental design. The mice were exposed to a 45% fat diet for combinations of three periods in life; (1) in utero, via the dams, (2) from birth to weaning, via milk during nursing, or (3) from weaning at 3 weeks to termination at 11 weeks of age (for Min/+ mice) or 23 weeks (for wild-type mice), to determine the most susceptible exposure period for development of obesity and intestinal tumorigenesis as adults. The effects of a 45% fat diet were studied on spontaneous tumorigenesis induced by the inherited mutation in the Apc gene and on tumors induced by the the food mutagen and carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). The mice in two experimental groups (marked with arrows) were given one s.c. injection of 25 mg/kg body weight of PhIP on days 3–6 after birth. In total, eight experimental groups were included in this experiment; a 10% fat diet throughout life as a negative control (10+10+10), a 45% fat diet in utero (45+10+10), a 45% fat diet during the nursing period (10+45+10), a 45% fat diet both in utero and during nursing (45+45+10), exposed to PhIP or not, a 45% fat diet as adults (10+10+45), or a 45% fat diet throughout life (45+45+45), exposed to PhIP or not.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4383426&req=5

fig1: Experimental design. The mice were exposed to a 45% fat diet for combinations of three periods in life; (1) in utero, via the dams, (2) from birth to weaning, via milk during nursing, or (3) from weaning at 3 weeks to termination at 11 weeks of age (for Min/+ mice) or 23 weeks (for wild-type mice), to determine the most susceptible exposure period for development of obesity and intestinal tumorigenesis as adults. The effects of a 45% fat diet were studied on spontaneous tumorigenesis induced by the inherited mutation in the Apc gene and on tumors induced by the the food mutagen and carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). The mice in two experimental groups (marked with arrows) were given one s.c. injection of 25 mg/kg body weight of PhIP on days 3–6 after birth. In total, eight experimental groups were included in this experiment; a 10% fat diet throughout life as a negative control (10+10+10), a 45% fat diet in utero (45+10+10), a 45% fat diet during the nursing period (10+45+10), a 45% fat diet both in utero and during nursing (45+45+10), exposed to PhIP or not, a 45% fat diet as adults (10+10+45), or a 45% fat diet throughout life (45+45+45), exposed to PhIP or not.
Mentions: Diets of purified ingredients from Research Diets Inc. (New Brunswick, NJ, USA) were used. The D12451 diet, containing 20%, 35%, and 45% of kcal from protein, carbohydrates, and fat, respectively, was used as a high fat diet. The D12450H diet, containing 20%, 70%, and 10% of kcal from protein, carbohydrates, and fat, respectively, was used as a matching control low fat diet. The amount of sucrose was 17% of the calories in both diets. The high fat diet had 4.73 kcal/g, whereas the low fat diet had 3.85 kcal/g; that is, the high fat diet contained 22.9% more kcal per gram diet. In order to avoid that the dietary treatment was unevenly spread out in time, we gave the first dam 10% fat diet, the second dam 45% fat diet, the third dam 10% fat diet, the forth dam 45% fat diet, and so on. Similarly, the litters of offspring were given either of the two diets after birth every other time and after weaning every other time until the necessary numbers in all experimental dietary groups were obtained (Figure 1). The number of litters (given in parentheses) in each treatment group was 10% fat diet throughout life (17), 45% fat diet in utero (17), 45% fat diet during the nursing period (14), 45% fat diet in utero and during the nursing period (19), 45% fat diet as adults (18), and 45% fat diet throughout life (21). For the groups also given PhIP, the number of litters was 45% fat diet in utero and during the nursing period (17) and 45% fat diet throughout life (17). The number of mice in each treatment group is given in the figures and tables for the various end points.

Bottom Line: We studied how obesogenic conditions during various life periods affected obesity and intestinal tumorigenesis in adult C57BL/6J-Min (multiple intestinal neoplasia)/+ mice.In the glucose tolerance test, the early exposure to a 45% fat diet in utero, during nursing, or during both in utero and nursing, did not affect blood glucose, whereas a 45% fat diet given to adults or throughout life did.The intrauterine and nursing period is a window of susceptibility for dietary fat-induced obesity and intestinal tumor development.

View Article: PubMed Central - PubMed

Affiliation: Department of Food, Water and Cosmetics, Division of Environmental Medicine, Norwegian Institute of Public Health, P.O. Box 4404 Nydalen, 0403 Oslo, Norway.

ABSTRACT
We studied how obesogenic conditions during various life periods affected obesity and intestinal tumorigenesis in adult C57BL/6J-Min (multiple intestinal neoplasia)/+ mice. The mice were given a 10% fat diet throughout life (negative control) or a 45% fat diet in utero, during nursing, during both in utero and nursing, during adult life, or during their whole life-span, and terminated at 11 weeks for tumorigenesis (Min/+) or 23 weeks for obesogenic effect (wild-type). Body weight at 11 weeks was increased after a 45% fat diet during nursing, during both in utero and nursing, and throughout life, but had normalized at 23 weeks. In the glucose tolerance test, the early exposure to a 45% fat diet in utero, during nursing, or during both in utero and nursing, did not affect blood glucose, whereas a 45% fat diet given to adults or throughout life did. However, a 45% fat diet during nursing or during in utero and nursing increased the number of small intestinal tumors. So did exposures to a 45% fat diet in adult life or throughout life, but without increasing the tumor numbers further. The intrauterine and nursing period is a window of susceptibility for dietary fat-induced obesity and intestinal tumor development.

Show MeSH
Related in: MedlinePlus