Caloric Restriction and Hypothalamic Leptin Gene Therapy Have Differential Effects on Energy Partitioning in Adult Female Rats
Dieting is a common but often ineffective long-term strategy for preventing weight gain. Similar to humans, adult rats exhibit progressive weight gain. The adipokine leptin regulates appetite and energy expenditure but hyperleptinemia is associated with leptin resistance. Here, we compared the effec...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/13/6789 |
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| author | Russell T. Turner Carmen P. Wong Kristina M. Fosse Adam J. Branscum Urszula T. Iwaniec |
| author_facet | Russell T. Turner Carmen P. Wong Kristina M. Fosse Adam J. Branscum Urszula T. Iwaniec |
| author_sort | Russell T. Turner |
| collection | DOAJ |
| description | Dieting is a common but often ineffective long-term strategy for preventing weight gain. Similar to humans, adult rats exhibit progressive weight gain. The adipokine leptin regulates appetite and energy expenditure but hyperleptinemia is associated with leptin resistance. Here, we compared the effects of increasing leptin levels in the hypothalamus using gene therapy with conventional caloric restriction on weight gain, food consumption, serum leptin and adiponectin levels, white adipose tissue, marrow adipose tissue, and bone in nine-month-old female Sprague-Dawley rats. Rats (<i>n</i> = 16) were implanted with a cannula in the 3rd ventricle of the hypothalamus and injected with a recombinant adeno-associated virus, encoding the rat gene for leptin (rAAV-<i>Lep</i>), and maintained on standard rat chow for 18 weeks. A second group (<i>n</i> = 15) was calorically-restricted to match the weight of the rAAV-<i>Lep</i> group. Both approaches prevented weight gain, and no differences in bone were detected. However, calorically-restricted rats consumed 15% less food and had lower brown adipose tissue <i>Ucp-1</i> mRNA expression than rAAV-<i>Lep</i> rats. Additionally, calorically-restricted rats had higher abdominal white adipose tissue mass, higher serum leptin and adiponectin levels, and higher marrow adiposity. Caloric restriction and hypothalamic leptin gene therapy, while equally effective in preventing weight gain, differ in their effects on energy intake, energy expenditure, adipokine levels, and body composition. |
| first_indexed | 2024-03-10T10:05:31Z |
| format | Article |
| id | doaj.art-5a772f6107d444e3ac5362406e7826cb |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T10:05:31Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-5a772f6107d444e3ac5362406e7826cb2023-11-22T01:34:16ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-06-012213678910.3390/ijms22136789Caloric Restriction and Hypothalamic Leptin Gene Therapy Have Differential Effects on Energy Partitioning in Adult Female RatsRussell T. Turner0Carmen P. Wong1Kristina M. Fosse2Adam J. Branscum3Urszula T. Iwaniec4Skeletal Biology Laboratory, School of Biological and Population Health Sciences, Oregon State University, Corvallis, OR 97331, USASkeletal Biology Laboratory, School of Biological and Population Health Sciences, Oregon State University, Corvallis, OR 97331, USASkeletal Biology Laboratory, School of Biological and Population Health Sciences, Oregon State University, Corvallis, OR 97331, USABiostatistics Program, School of Biological and Population Health Sciences, Oregon State University, Corvallis, OR 97331, USASkeletal Biology Laboratory, School of Biological and Population Health Sciences, Oregon State University, Corvallis, OR 97331, USADieting is a common but often ineffective long-term strategy for preventing weight gain. Similar to humans, adult rats exhibit progressive weight gain. The adipokine leptin regulates appetite and energy expenditure but hyperleptinemia is associated with leptin resistance. Here, we compared the effects of increasing leptin levels in the hypothalamus using gene therapy with conventional caloric restriction on weight gain, food consumption, serum leptin and adiponectin levels, white adipose tissue, marrow adipose tissue, and bone in nine-month-old female Sprague-Dawley rats. Rats (<i>n</i> = 16) were implanted with a cannula in the 3rd ventricle of the hypothalamus and injected with a recombinant adeno-associated virus, encoding the rat gene for leptin (rAAV-<i>Lep</i>), and maintained on standard rat chow for 18 weeks. A second group (<i>n</i> = 15) was calorically-restricted to match the weight of the rAAV-<i>Lep</i> group. Both approaches prevented weight gain, and no differences in bone were detected. However, calorically-restricted rats consumed 15% less food and had lower brown adipose tissue <i>Ucp-1</i> mRNA expression than rAAV-<i>Lep</i> rats. Additionally, calorically-restricted rats had higher abdominal white adipose tissue mass, higher serum leptin and adiponectin levels, and higher marrow adiposity. Caloric restriction and hypothalamic leptin gene therapy, while equally effective in preventing weight gain, differ in their effects on energy intake, energy expenditure, adipokine levels, and body composition.https://www.mdpi.com/1422-0067/22/13/6789obesitymarrow adipose tissuewhite adipose tissue<i>Ucp-1</i>leptinadiponectin |
| spellingShingle | Russell T. Turner Carmen P. Wong Kristina M. Fosse Adam J. Branscum Urszula T. Iwaniec Caloric Restriction and Hypothalamic Leptin Gene Therapy Have Differential Effects on Energy Partitioning in Adult Female Rats International Journal of Molecular Sciences obesity marrow adipose tissue white adipose tissue <i>Ucp-1</i> leptin adiponectin |
| title | Caloric Restriction and Hypothalamic Leptin Gene Therapy Have Differential Effects on Energy Partitioning in Adult Female Rats |
| title_full | Caloric Restriction and Hypothalamic Leptin Gene Therapy Have Differential Effects on Energy Partitioning in Adult Female Rats |
| title_fullStr | Caloric Restriction and Hypothalamic Leptin Gene Therapy Have Differential Effects on Energy Partitioning in Adult Female Rats |
| title_full_unstemmed | Caloric Restriction and Hypothalamic Leptin Gene Therapy Have Differential Effects on Energy Partitioning in Adult Female Rats |
| title_short | Caloric Restriction and Hypothalamic Leptin Gene Therapy Have Differential Effects on Energy Partitioning in Adult Female Rats |
| title_sort | caloric restriction and hypothalamic leptin gene therapy have differential effects on energy partitioning in adult female rats |
| topic | obesity marrow adipose tissue white adipose tissue <i>Ucp-1</i> leptin adiponectin |
| url | https://www.mdpi.com/1422-0067/22/13/6789 |
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