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Author |
Jeong, S.; Han, M.; Lee, H.; Kim, M.; Kim, J.; Nicol, C.J.; Kim, B.H.; Choi, J.H.; Nam, K.-H.; Oh, G.T.; Yoon, M. |
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Title |
Effects of fenofibrate on high-fat diet-induced body weight gain and adiposity in female C57BL/6J mice |
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Journal Article |
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Year |
2004 |
Publication |
Metabolism: clinical and experimental |
Abbreviated Journal |
Metabolism |
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Volume |
53 |
Issue |
10 |
Pages |
1284-1289 |
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Keywords |
Adipose Tissue/*anatomy & histology/drug effects; Animals; Antilipemic Agents/*pharmacology; Body Composition/*drug effects; Body Weight/drug effects; Dietary Fats/*pharmacology; Eating/drug effects; Fatty Acids/metabolism; Female; Gene Expression Regulation/drug effects; Leptin/metabolism; Liver/metabolism; Mice; Mice, Inbred C57BL; Ovariectomy; Procetofen/*pharmacology; RNA, Messenger/biosynthesis/genetics; Receptors, Cytoplasmic and Nuclear/biosynthesis/genetics/metabolism; Transcription Factors/biosynthesis/genetics/metabolism; Weight Gain/*drug effects |
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Abstract |
Our previous study suggested that fenofibrate affects obesity and lipid metabolism in a sexually dimorphic manner in part through the differential activation of hepatic peroxisome proliferator-activated receptor alpha (PPARalpha) in male and female C57BL/6J mice. To determine whether fenofibrate reduces body weight gain and adiposity in female sham-operated (Sham) and ovariectomized (OVX) C57BL/6J mice, the effects of fenofibrate on not only body weight, white adipose tissue (WAT) mass, and food intake, but also the expression of both leptin and PPARalpha target genes were measured. Compared to their respective low-fat diet-fed controls, both Sham and OVX mice exhibited increases in body weight and WAT mass when fed a high-fat diet. Fenofibrate treatment decreased body weight gain and WAT mass in OVX, but not in Sham mice. Furthermore, fenofibrate increased the mRNA levels of PPARalpha target genes encoding peroxisomal enzymes involved in fatty acid beta-oxidation, and reduced apolipoprotein C-III (apo C-III) mRNA, all of which were expressed at higher levels in OVX compared to Sham mice. However, leptin mRNA levels were found to positively correlate with WAT mass, and food intake was not changed in either OVX or Sham mice following fenofibrate treatment. These results suggest that fenofibrate differentially regulates body weight and adiposity due in part to differences in PPARalpha activation, but not to differences in leptin production, between female OVX and Sham mice. |
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Department of Life Sciences, Mokwon University, Taejon, Korea |
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English |
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0026-0495 |
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Notes |
PMID:15375783 |
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Call Number |
refbase @ user @ |
Serial |
72 |
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Author |
Nicol, C.J.; Yoon, M.; Ward, J.M.; Yamashita, M.; Fukamachi, K.; Peters, J.M.; Gonzalez, F.J. |
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Title |
PPARgamma influences susceptibility to DMBA-induced mammary, ovarian and skin carcinogenesis |
Type |
Journal Article |
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Year |
2004 |
Publication |
Carcinogenesis |
Abbreviated Journal |
Carcinogenesis |
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Volume |
25 |
Issue |
9 |
Pages |
1747-1755 |
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Keywords |
9,10-Dimethyl-1,2-benzanthracene/*toxicity; Animals; DNA Primers/chemistry; Disease Susceptibility; Female; Heterozygote; Humans; Mammary Neoplasms, Experimental/chemically induced/*pathology; Mice; Ovarian Neoplasms/chemically induced/*pathology; RNA, Messenger/genetics/metabolism; Receptors, Cytoplasmic and Nuclear/genetics/*physiology; Reverse Transcriptase Polymerase Chain Reaction; Skin Neoplasms/chemically induced/*pathology; Survival Rate; Transcription Factors/genetics/*physiology; Zinc Fingers |
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Abstract |
Peroxisome proliferator-activated receptor gamma (PPARgamma), a member of the nuclear receptor superfamily, plays a role in adipocyte differentiation, type II diabetes, macrophage response to inflammation and is suggested to influence carcinogen-induced colon cancer. Studies done in vitro and in vivo also revealed that PPARgamma ligands might promote differentiation and/or regression of mammary tumors. To directly evaluate the role of PPARgamma in mammary carcinogenesis, PPARgamma wild-type (+/+) or heterozygous (+/-) mice were administered 1 mg 7,12-dimethylbenz[a]anthracene (DMBA) by gavage once a week for 6 weeks and followed for a total of 25 weeks. Compared with congenic PPARgamma(+/+) littermate controls, PPARgamma(+/-) mice had early evidence for increased susceptibility to DMBA-mediated carcinogenesis based on a 1.6-fold increase in the percentage of mice with skin papillomas, as well as a 1.7-fold increase in the numbers of skin papillomas per mouse (P < 0.05). Similarly, PPARgamma(+/-) mice also had a 1.5-fold decreased survival rate (P = 0.059), and a 1.7-fold increased incidence of total tumors per mouse (P < 0.01). Moreover, PPARgamma(+/-) mice had an almost 3-fold increase in mammary adenocarcinomas (P < 0.05), an over 3-fold increase in ovarian granulosa cell carcinomas (P < 0.05), an over 3-fold increase in malignant tumors (P < 0.02) and a 4.6-fold increase in metastatic incidence. These results are the first to demonstrate an increased susceptibility in vivo of PPARgamma haploinsufficiency to DMBA-mediated carcinogenesis and suggest that PPARgamma may act as a tumor modifier of skin, ovarian and breast cancers. The data also support evidence suggesting a beneficial role for PPARgamma-specific ligands in the chemoprevention of mammary, ovarian and skin carcinogenesis. |
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Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA |
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0143-3334 |
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Notes |
PMID:15073042 |
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refbase @ user @ |
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76 |
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Permanent link to this record |