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Genetic and Diet-Induced Obesity Increased Intestinal Tumorigenesis in the Double Mutant Mouse Model Multiple Intestinal Neoplasia X Obese via Disturbed Glucose Regulation and Inflammation.

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

Bottom Line: Except for bw, ob/wt and wt/wt were not significantly different.A 45% fat diet further increased glucose, but not insulin.Thus the results implicate disturbed glucose regulation and inflammation as mechanisms involved in the association between obesity and intestinal tumorigenesis.

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 have studied how spontaneous or carcinogen-induced intestinal tumorigenesis was affected by genetic or diet-induced obesity in C57BL/6J-Apc (Min/+) X C57BL/6J-Lep (ob/+) mice. Obesity was induced by the obese (ob) mutation in the lep gene coding for the hormone leptin, or by a 45% fat diet. The effects of obesity were examined on spontaneous intestinal tumors caused by the multiple intestinal neoplasia (Min) mutation in the adenomatous polyposis coli (Apc) gene and on tumors induced by the dietary carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). F1 ob/ob (homozygous mutated) mice had increased body weight (bw) and number of spontaneous and PhIP-induced small intestinal tumors (in Apc (Min/+) mice), versus ob/wt (heterozygous mutated) and wt/wt mice (homozygous wild-type). A 45% fat diet exacerbated bw and spontaneous tumor numbers versus 10% fat, but not PhIP-induced tumors. Except for bw, ob/wt and wt/wt were not significantly different. The obesity caused hyperglucosemia and insulinemia in ob/ob mice. A 45% fat diet further increased glucose, but not insulin. Inflammation was seen as increased TNFα levels in ob/ob mice. Thus the results implicate disturbed glucose regulation and inflammation as mechanisms involved in the association between obesity and intestinal tumorigenesis. Ob/ob mice had shorter lifespan than ob/wt and wt/wt mice.

No MeSH data available.


Related in: MedlinePlus

Body weight as area under the curve (AUC). Body weight was recorded weekly from weaning at week 3 until termination at week 11 and is presented for ApcMin/+ (a) females and (b) males, and Apc+/+ (c) females and (d) males (mean ± SD). The mice were exposed to 0.9% NaCl and given a 10% fat diet (white columns) or 0.9% NaCl and a 45% fat diet (light grey columns), or they were exposed to PhIP and given a 10% fat diet (dark grey columns) or PhIP and a 45% fat diet (black columns). n = 10–18 mice. a.u. = arbitrary units.
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fig1: Body weight as area under the curve (AUC). Body weight was recorded weekly from weaning at week 3 until termination at week 11 and is presented for ApcMin/+ (a) females and (b) males, and Apc+/+ (c) females and (d) males (mean ± SD). The mice were exposed to 0.9% NaCl and given a 10% fat diet (white columns) or 0.9% NaCl and a 45% fat diet (light grey columns), or they were exposed to PhIP and given a 10% fat diet (dark grey columns) or PhIP and a 45% fat diet (black columns). n = 10–18 mice. a.u. = arbitrary units.

Mentions: Body weight was compared between the treatment groups (n = 10–18) by calculating the area under the curve (AUC) for the body weight development from weaning at week 3 to termination at week 11 (Figure 1). For this end point, data from both ApcMin/+ and Apc+/+ were evaluated. The ApcMin/+ mice were lighter than the Apc+/+ mice (P < 0.001). There were no differences between mice treated with 0.9% NaCl or PhIP, based on all mice and in the subgroups ob/ob, ob/wt, and wt/wt mice. AUC was higher for males than females based on all mice (P < 0.001), in the subgroups ob/ob, ob/wt, and wt/wt mice (P < 0.001, for all three comparisons), and in all three ob genotypes on a 45% fat diet and for ob/wt and wt/wt on a 10% fat diet (P < 0.001, for all comparisons), but not for ob/ob mice on a 10% fat diet.


Genetic and Diet-Induced Obesity Increased Intestinal Tumorigenesis in the Double Mutant Mouse Model Multiple Intestinal Neoplasia X Obese via Disturbed Glucose Regulation and Inflammation.

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

Body weight as area under the curve (AUC). Body weight was recorded weekly from weaning at week 3 until termination at week 11 and is presented for ApcMin/+ (a) females and (b) males, and Apc+/+ (c) females and (d) males (mean ± SD). The mice were exposed to 0.9% NaCl and given a 10% fat diet (white columns) or 0.9% NaCl and a 45% fat diet (light grey columns), or they were exposed to PhIP and given a 10% fat diet (dark grey columns) or PhIP and a 45% fat diet (black columns). n = 10–18 mice. a.u. = arbitrary units.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4546984&req=5

fig1: Body weight as area under the curve (AUC). Body weight was recorded weekly from weaning at week 3 until termination at week 11 and is presented for ApcMin/+ (a) females and (b) males, and Apc+/+ (c) females and (d) males (mean ± SD). The mice were exposed to 0.9% NaCl and given a 10% fat diet (white columns) or 0.9% NaCl and a 45% fat diet (light grey columns), or they were exposed to PhIP and given a 10% fat diet (dark grey columns) or PhIP and a 45% fat diet (black columns). n = 10–18 mice. a.u. = arbitrary units.
Mentions: Body weight was compared between the treatment groups (n = 10–18) by calculating the area under the curve (AUC) for the body weight development from weaning at week 3 to termination at week 11 (Figure 1). For this end point, data from both ApcMin/+ and Apc+/+ were evaluated. The ApcMin/+ mice were lighter than the Apc+/+ mice (P < 0.001). There were no differences between mice treated with 0.9% NaCl or PhIP, based on all mice and in the subgroups ob/ob, ob/wt, and wt/wt mice. AUC was higher for males than females based on all mice (P < 0.001), in the subgroups ob/ob, ob/wt, and wt/wt mice (P < 0.001, for all three comparisons), and in all three ob genotypes on a 45% fat diet and for ob/wt and wt/wt on a 10% fat diet (P < 0.001, for all comparisons), but not for ob/ob mice on a 10% fat diet.

Bottom Line: Except for bw, ob/wt and wt/wt were not significantly different.A 45% fat diet further increased glucose, but not insulin.Thus the results implicate disturbed glucose regulation and inflammation as mechanisms involved in the association between obesity and intestinal tumorigenesis.

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 have studied how spontaneous or carcinogen-induced intestinal tumorigenesis was affected by genetic or diet-induced obesity in C57BL/6J-Apc (Min/+) X C57BL/6J-Lep (ob/+) mice. Obesity was induced by the obese (ob) mutation in the lep gene coding for the hormone leptin, or by a 45% fat diet. The effects of obesity were examined on spontaneous intestinal tumors caused by the multiple intestinal neoplasia (Min) mutation in the adenomatous polyposis coli (Apc) gene and on tumors induced by the dietary carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). F1 ob/ob (homozygous mutated) mice had increased body weight (bw) and number of spontaneous and PhIP-induced small intestinal tumors (in Apc (Min/+) mice), versus ob/wt (heterozygous mutated) and wt/wt mice (homozygous wild-type). A 45% fat diet exacerbated bw and spontaneous tumor numbers versus 10% fat, but not PhIP-induced tumors. Except for bw, ob/wt and wt/wt were not significantly different. The obesity caused hyperglucosemia and insulinemia in ob/ob mice. A 45% fat diet further increased glucose, but not insulin. Inflammation was seen as increased TNFα levels in ob/ob mice. Thus the results implicate disturbed glucose regulation and inflammation as mechanisms involved in the association between obesity and intestinal tumorigenesis. Ob/ob mice had shorter lifespan than ob/wt and wt/wt mice.

No MeSH data available.


Related in: MedlinePlus