An intrinsic gut leptin-melanocortin pathway modulates intestinal microsomal triglyceride transfer protein and lipid absorption
Fat is delivered to tissues by apoB-containing lipoproteins synthesized in the liver and intestine with the help of an intracellular chaperone, microsomal triglyceride transfer protein (MTP). Leptin, a hormone secreted by adipose tissue, acts in the brain and on peripheral tissues to regulate fat st...
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| Format: | Article |
| Language: | English |
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Elsevier
2010-07-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520371157 |
| _version_ | 1818930817280245760 |
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| author | Jahangir Iqbal Xiaosong Li Benny Hung-Junn Chang Lawrence Chan Gary J. Schwartz Streamson C. Chua, Jr. M. Mahmood Hussain |
| author_facet | Jahangir Iqbal Xiaosong Li Benny Hung-Junn Chang Lawrence Chan Gary J. Schwartz Streamson C. Chua, Jr. M. Mahmood Hussain |
| author_sort | Jahangir Iqbal |
| collection | DOAJ |
| description | Fat is delivered to tissues by apoB-containing lipoproteins synthesized in the liver and intestine with the help of an intracellular chaperone, microsomal triglyceride transfer protein (MTP). Leptin, a hormone secreted by adipose tissue, acts in the brain and on peripheral tissues to regulate fat storage and metabolism. Our aim was to identify the role of leptin signaling in MTP regulation and lipid absorption using several mouse models deficient in leptin receptor (LEPR) signaling and downstream effectors. Mice with spontaneous LEPR B mutations or targeted ablation of LEPR B in proopiomelanocortin (POMC) or agouti gene related peptide (AGRP) expressing cells had increased triglyceride in plasma, liver, and intestine. Furthermore, melanocortin 4 receptor (MC4R) knockout mice expressed a similar triglyceride phenotype, suggesting that leptin might regulate intestinal MTP expression through the melanocortin pathway. Mechanistic studies revealed that the accumulation of triglyceride in the intestine might be secondary to decreased expression of MTP and lipid absorption in these mice. Surgical and chemical blockade of vagal efferent outflow to the intestine in wild-type mice failed to alter the triglyceride phenotype, demonstrating that central neural control mechanisms were likely not involved in the observed regulation of intestinal MTP. Instead, we found that enterocytes express LEPR, POMC, AGRP, and MC4R. We propose that a peripheral, local gut signaling mechanism involving LEPR B and MC4R regulates intestinal MTP and controls intestinal lipid absorption. |
| first_indexed | 2024-12-20T04:06:43Z |
| format | Article |
| id | doaj.art-4f525c3e5c6c49138dbb00215678677c |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-20T04:06:43Z |
| publishDate | 2010-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-4f525c3e5c6c49138dbb00215678677c2022-12-21T19:54:01ZengElsevierJournal of Lipid Research0022-22752010-07-0151719291942An intrinsic gut leptin-melanocortin pathway modulates intestinal microsomal triglyceride transfer protein and lipid absorptionJahangir Iqbal0Xiaosong Li1Benny Hung-Junn Chang2Lawrence Chan3Gary J. Schwartz4Streamson C. Chua, Jr.5M. Mahmood Hussain6Department of Cell Biology and Pediatrics, State University of New York Health Science Center at Brooklyn (SUNY Downstate Medical Center), Brooklyn, NYDepartment of Medicine and Neuroscience, Albert Einstein College of Medicine, Bronx, NYDepartment of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TXDepartment of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TXDepartment of Medicine and Neuroscience, Albert Einstein College of Medicine, Bronx, NYDepartment of Medicine and Neuroscience, Albert Einstein College of Medicine, Bronx, NYTo whom correspondence should be addressed; Department of Cell Biology and Pediatrics, State University of New York Health Science Center at Brooklyn (SUNY Downstate Medical Center), Brooklyn, NYFat is delivered to tissues by apoB-containing lipoproteins synthesized in the liver and intestine with the help of an intracellular chaperone, microsomal triglyceride transfer protein (MTP). Leptin, a hormone secreted by adipose tissue, acts in the brain and on peripheral tissues to regulate fat storage and metabolism. Our aim was to identify the role of leptin signaling in MTP regulation and lipid absorption using several mouse models deficient in leptin receptor (LEPR) signaling and downstream effectors. Mice with spontaneous LEPR B mutations or targeted ablation of LEPR B in proopiomelanocortin (POMC) or agouti gene related peptide (AGRP) expressing cells had increased triglyceride in plasma, liver, and intestine. Furthermore, melanocortin 4 receptor (MC4R) knockout mice expressed a similar triglyceride phenotype, suggesting that leptin might regulate intestinal MTP expression through the melanocortin pathway. Mechanistic studies revealed that the accumulation of triglyceride in the intestine might be secondary to decreased expression of MTP and lipid absorption in these mice. Surgical and chemical blockade of vagal efferent outflow to the intestine in wild-type mice failed to alter the triglyceride phenotype, demonstrating that central neural control mechanisms were likely not involved in the observed regulation of intestinal MTP. Instead, we found that enterocytes express LEPR, POMC, AGRP, and MC4R. We propose that a peripheral, local gut signaling mechanism involving LEPR B and MC4R regulates intestinal MTP and controls intestinal lipid absorption.http://www.sciencedirect.com/science/article/pii/S0022227520371157MTPapoBfat absorptionleptin receptorPOMCAGRP |
| spellingShingle | Jahangir Iqbal Xiaosong Li Benny Hung-Junn Chang Lawrence Chan Gary J. Schwartz Streamson C. Chua, Jr. M. Mahmood Hussain An intrinsic gut leptin-melanocortin pathway modulates intestinal microsomal triglyceride transfer protein and lipid absorption Journal of Lipid Research MTP apoB fat absorption leptin receptor POMC AGRP |
| title | An intrinsic gut leptin-melanocortin pathway modulates intestinal microsomal triglyceride transfer protein and lipid absorption |
| title_full | An intrinsic gut leptin-melanocortin pathway modulates intestinal microsomal triglyceride transfer protein and lipid absorption |
| title_fullStr | An intrinsic gut leptin-melanocortin pathway modulates intestinal microsomal triglyceride transfer protein and lipid absorption |
| title_full_unstemmed | An intrinsic gut leptin-melanocortin pathway modulates intestinal microsomal triglyceride transfer protein and lipid absorption |
| title_short | An intrinsic gut leptin-melanocortin pathway modulates intestinal microsomal triglyceride transfer protein and lipid absorption |
| title_sort | intrinsic gut leptin melanocortin pathway modulates intestinal microsomal triglyceride transfer protein and lipid absorption |
| topic | MTP apoB fat absorption leptin receptor POMC AGRP |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520371157 |
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