HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Interpretive Summary Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Suhara, W. Articles by Kojo, H. PubMed PubMed Citation Articles by Suhara, W. Articles by Kojo, H.

Cow’s milk increases the activities of human nuclear receptors peroxisome proliferator-activated receptors and and retinoid X receptor involved in the regulation of energy homeostasis, obesity, and inflammation

W. Suhara^*, H. Koide^*,, T. Okuzawa^*, D. Hayashi, T. Hashimoto and H. Kojo^*,,1

^* Institute Oncorex Inc., Sapporo, Hokkaido 060-0063, Japan
Theravalues Corporation, Tokyo 102-0094, Japan

¹ Corresponding author: hkojo{at}theravalues.com

The nuclear peroxisome proliferator-activated receptors (PPAR) have been shown to play crucial roles in regulating energy homeostasis including lipid and carbohydrate metabolism, inflammatory responses, and cell proliferation, differentiation, and survival. Because PPAR agonists have the potential to prevent or ameliorate diseases such as hyperlipidemia, diabetes, atherosclerosis, and obesity, we have explored new natural agonists for PPAR. For this purpose, cow’s milk was tested for agonistic activity toward human PPAR subtypes using a reporter gene assay. Milk increased human PPAR activity in a dose-dependent manner with a 3.2-fold increase at 0.5% (vol/vol). It also enhanced human PPAR activity in a dose-dependent manner with an 11.5-fold increase at 0.5%. However, it only slightly affected human PPAR activity. Ice cream, butter, and yogurt also increased the activities of PPAR and PPAR, whereas vegetable cream affected activity of PPAR but not PPAR. Skim milk enhanced the activity of PPAR to a lesser degree than regular milk. Milk and fresh cream increased the activity of human retinoid X receptor (RXR) as well as PPAR and PPAR, whereas neither affected vitamin D3 receptor, estrogen receptors and β, or thyroid receptors and β. Both milk and fresh cream were shown by quantitative real-time PCR to increase the quantity of mRNA for uncoupling protein 2 (UCP2), an energy expenditure gene, in a dose-dependent manner. The increase in UCP2 mRNA was found to be reduced by treatment with PPAR-short interfering (si)RNA. This study unambiguously clarified at the cellular level that cow’s milk increased the activities of human PPAR, PPAR, and RXR. The possible role in enhancing the activities of PPAR, PPAR, and RXR, and the health benefits of cow’s milk were discussed.

Key Words: milk • peroxisome proliferator-activated receptor • peroxisome proliferator-activated receptor • retinoid X receptor