Leptin Rapidly Lowers Food Intake and Elevates Metabolic Rates in Lean and ob/ob Mice ,
Open accessAbstract
Leptin, the ob gene product, is released from adipose tissue and likely acts in the central nervous system, particularly within the hypothalamus, to exert many of its effects. Obesity in C57BL/6J ob/ob mice is caused by a mutation in the ob gene resulting in a lack of functional leptin. In this study, we first compared effects of a single intracerebroventricular (ICV) injection of 3 pmol (50 ng) or 60 pmol (1 microg) leptin on food intake and oxygen consumption of lean and ob/ob mice deprived of food for 4 h during the 48-h period postinjection. Injection of 3 pmol leptin minimally lowered food intake in these mice without influencing oxygen consumption. Injection of 60 pmol of leptin rapidly lowered food intake within 30 min in both lean and ob/ob mice, with effects persisting for 24 h. Lean and ob/ob mice treated with leptin consumed 40 and 60% less food, respectively, in 24 h than vehicle-treated controls. Injection of leptin (60 pmol ICV) suppressed food intake of adrenalectomized mice as well (by 25 and 40% in lean mice and by 20 and 68% in ob/ob mice at 3 and 24 h, respectively), indicating that glucocorticoids are not essential for leptin to suppress food intake. Leptin increased oxygen consumption in conditions in which diet-induced thermogenesis was low, i.e., in fed ob/ob mice and in food-deprived lean mice, but not in fed adrenalectomized ob/ob mice or in fed lean mice. ICV injection of 60 pmol leptin along with 230 pmol (2 microg) of neuropeptide Y (NPY) attenuated NPY-induced feeding in ob/ob, but not in lean mice, suggesting an enhanced potential for crosstalk between the leptin and NPY signaling systems in ob/ob mice lacking endogenous leptin. Leptin exerts rapid-onset actions within the central nervous system to coordinate control of food intake and metabolic rate.
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To date there is limited evidence that leptin mediates thermogenesis via the SNS in humans.
“In addition, leptin, released by white adipocytes, regulates energy balance by effects on the hypothalamus that lead to inhibition of food intake and increased thermogenesis via activation of the SNS, though to date there is limited evidence that leptin mediates thermogenesis via the SNS in humans 66–70.”
From Cellular bioenergetics as a target for obesity therapy (2010) · cites this paper as [66]
Leptin, released by white adipocytes, regulates energy balance by effects on the hypothalamus that lead to inhibition of food intake and increased thermogenesis via activation of the SNS.
“In addition, leptin, released by white adipocytes, regulates energy balance by effects on the hypothalamus that lead to inhibition of food intake and increased thermogenesis via activation of the SNS, though to date there is limited evidence that leptin mediates thermogenesis via the SNS in humans 66–70.”
From Cellular bioenergetics as a target for obesity therapy (2010) · cites this paper as [66]
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Cites
Baltosser, W. H., & Zar, J. H. (1996) · Ecology · doi:10.2307/2265725 · Cited by 35,166 · see citing works
Positional cloning of the mouse obese gene and its human homologue
Zhang, Y., Proenca, R., Maffei, M., Barone, M., Leopold, L., & Friedman, J. M. (1994) · Nature · doi:10.1038/372425a0 · Cited by 13,419 · see citing works
Weight-Reducing Effects of the Plasma Protein Encoded by the <i>obese</i> Gene
Halaas, J. L., Gajiwala, K. S., Maffei, M., Cohen, S. L., Chait, B. T., Rabinowitz, D., Lallone, R. L., Burley, S. K., & Friedman, J. M. (1995) · Science · doi:10.1126/science.7624777 · Cited by 4,451 · see citing works
Effects of the <i>obese</i> Gene Product on Body Weight Regulation in <i>ob</i> / <i>ob</i> Mice
Pelleymounter, M. A., Cullen, M. J., Baker, M. B., Hecht, R., Winters, D., Boone, T., & Collins, F. (1995) · Science · doi:10.1126/science.7624776 · Cited by 4,017 · see citing works
Campfield, L. A., Smith, F. J., Guisez, Y., Devos, R., & Burn, P. (1995) · Science · doi:10.1126/science.7624778 · Cited by 3,243 · see citing works
Abnormal splicing of the leptin receptor in diabetic mice
Lee, G.-H., Proenca, R., Montez, J. M., Carroll, K. M., Darvishzadeh, J. G., Lee, J. I., & Friedman, J. M. (1996) · Nature · doi:10.1038/379632a0 · Cited by 2,327 · see citing works
The role of neuropeptide Y in the antiobesity action of the obese gene product
Stephens, T. W., Basinski, M., Bristow, P. K., Bue-Valleskey, J. M., Burgett, S. G., Craft, L., Hale, J., Hoffmann, J., Hsiung, H. M., Kriauciunas, A., et al. (1995) · Nature · doi:10.1038/377530a0 · Cited by 1,498 · see citing works
Identification of targets of leptin action in rat hypothalamus.
Schwartz, M. W., Seeley, R. J., Campfield, L. A., Burn, P., & Baskin, D. G. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118891 · Cited by 1,475 · see citing works
Sensitivity to leptin and susceptibility to seizures of mice lacking neuropeptide Y
Erickson, J. C., Clegg, K. E., & Palmiter, R. D. (1996) · Nature · doi:10.1038/381415a0 · Cited by 1,009 · see citing works
Leptin: The Tale of an Obesity Gene
Caro, J. F., Sinha, M. K., Kolaczynski, J. W., Zhang, P. L., & Considine, R. V. (1996) · Diabetes · doi:10.2337/diab.45.11.1455 · Cited by 982 · see citing works
Schwartz, M. W., Baskin, D. G., Bukowski, T. R., Kuijper, J. L., Foster, D., Lasser, G., Prunkard, D. E., Porte, D., Woods, S. C., Seeley, R. J., et al. (1996) · Diabetes · doi:10.2337/diab.45.4.531 · Cited by 904 · see citing works
Defective STAT signaling by the leptin receptor in diabetic mice.
Ghilardi, N., Ziegler, S., Wiestner, A. C., Stoffel, R., Heim, M. H., & Skoda, R. C. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.13.6231 · Cited by 793 · see citing works
Role of leptin in fat regulation
Collins, S., Kuhn, C. M., Petro, A. E., Swick, A. G., Chrunyk, B. A., & Surwit, R. S. (1996) · Nature · doi:10.1038/380677a0 · Cited by 520 · see citing works
Self-citationVos, P. D., Saladin, R., Auwerx, J. H., & Staels, B. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.27.15958 · Cited by 469 · see citing works
Recombinant ob protein reduces feeding and body weight in the ob/ob mouse.
Weigle, D. S., Bukowski, T. R., Foster, D. C., Holderman, S. D., Kramer, J. M., Lasser, G. W., Lofton–Day, C., Prunkard, D. E., Raymond, C. K., & Kuijper, J. L. (1995) · Journal of Clinical Investigation · doi:10.1172/jci118254 · Cited by 420 · see citing works
Effects of intracerebroventricular injection of neuropeptide Y on energy metabolism
Billington, C. J., Briggs, J. E., Grace, M. K., & Levine, A. S. (1991) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1991.260.2.r321 · Cited by 412 · see citing works
Zakrzewska, K. E., Cusin, I., Sainsbury, A., Rohner‐Jeanrenaud, F., & Jeanrenaud, B. (1997) · Diabetes · doi:10.2337/diab.46.4.717 · Cited by 313 · see citing works
Wilding, J. P. H., Gilbey, S. G., Bailey, C. J., Batt, R. A., Williams, G., Ghatei, M. A., & Bloom, S. R. (1993) · Endocrinology · doi:10.1210/endo.132.5.7682936 · Cited by 285 · see citing works
Neuropeptide Y suppresses sympathetic activity to interscapular brown adipose tissue in rats
Egawa, M., Yoshimatsu, H., & Bray, G. A. (1991) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1991.260.2.r328 · Cited by 272 · see citing works
Central effects of CRF on metabolism and energy balance
Rothwell, N. J. (1990) · Neuroscience & Biobehavioral Reviews · doi:10.1016/s0149-7634(05)80037-5 · Cited by 189 · see citing works
Leptin, the obese gene product, rapidly modulates synaptic transmission in the hypothalamus.
Glaum, S. R., Hara, M., Bindokas, V. P., Lee, C. C., Polonsky, K. S., Bell, G. I., & Miller, R. J. (1996) · Molecular Pharmacology · doi:10.1016/s0026-895x(25)09211-9 · Cited by 173 · see citing works
Brain neuropeptide Y: An integrator of endocrine, metabolic and behavioral processes
LEIBOWITZ, S. F. (1991) · Brain Research Bulletin · doi:10.1016/0361-9230(91)90121-y · Cited by 147 · see citing works
Hwa, J., Ghibaudi, L., Compton, D. S., Fawzi, A. B., & Strader, C. D. (1996) · Hormone and Metabolic Research · doi:10.1055/s-2007-979873 · Cited by 131 · see citing works
Neuropeptide Y: a central regulator of energy homeostasis
White, J. D. (1993) · Regulatory Peptides · doi:10.1016/0167-0115(93)90431-7 · Cited by 123 · see citing works
Adrenalectomy increases norepinephrine turnover in brown adipose tissue of obese (ob/ob) mice
Tuig, J. G. V., Ohshima, K., Yoshida, T., Romsos, D. R., & Bray, G. A. (1984) · Life Sciences · doi:10.1016/0024-3205(84)90056-0 · Cited by 72 · see citing works
Self-citationFeeding inhibition by neuropeptide Y
Smith, F. J., Campfield, L. A., Moschera, J. A., Bailon, P., & Burn, P. (1996) · Nature · doi:10.1038/382307a0 · Cited by 66 · see citing works
Norepinephrine turnover in obese (ob/ob) mice: effects of age, fasting, and acute cold.
Knehans, A., & Romsos, D. (1983) · American Journal of Physiology · doi:10.1152/ajpendo.1983.244.6.e567 · Cited by 54 · see citing works
Self-citationHolt, S. J., & York, D. A. (1989) · Physiology & Behavior · doi:10.1016/0031-9384(89)90098-x · Cited by 50 · see citing works
Effects of intraventricular infusion of corticotropin-releasing factor on VMH-lesioned obese rats
Arase, K., Shargill, N. S., & Bray, G. A. (1989) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1989.256.3.r751 · Cited by 45 · see citing works
Chen, J., Rhee, K. K., Beaudry, D. M., et al. (2008) · Neuroendocrinology · doi:10.1159/000123918 · Cited by 32 · see citing works
Glucocorticoids in the CNS regulate BAT metabolism and plasma insulin in ob/ob mice
Walker, H. C., & Romsos, D. R. (1992) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1992.262.1.e110 · Cited by 30 · see citing works
Self-citationDrescher, V. S., Chen, H., & Romsos, D. R. (1994) · Journal of Nutrition · doi:10.1093/jn/124.4.524 · Cited by 29 · see citing works
Self-citationAdrenalectomy reverses pre-existing obesity in adult genetically obese (ob/ob) mice.
Feldkircher, K., Mistry, A., & Romsos, D. R. (1996) · PubMed · Cited by 28 · see citing works
Self-citationBrown adipose tissue metabolism in ob/ob mice: effects of a high-fat diet and adrenalectomy
Kim, H. K., & Romsos, D. R. (1987) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1987.253.2.e149 · Cited by 5 · see citing works
Self-citationMistry, A. M., Chen, N.-G., Lee, Y., et al. (1995) · Journal of Nutrition · doi:10.1093/jn/125.3.503 · Cited by 2 · see citing works
Self-citation
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Endoplasmic Reticulum Stress Plays a Central Role in Development of Leptin Resistance
Ozcan, L., Ergin, A. S., Lu, A., Chung, J., Sarkar, S., Nie, D., Myers, M. G., & Ozcan, U. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2008.12.004 · Cited by 875 · see citing works
Cellular bioenergetics as a target for obesity therapy
Tseng, Y.-H., Cypess, A. M., & Kahn, C. R. (2010) · Nature Reviews Drug Discovery · doi:10.1038/nrd3138 · Cited by 591 · see citing works
Kleinridders, A., Schenten, D., Könner, A. C., Belgardt, B. F., Mauer, J., Okamura, T., Wunderlich, F. T., Medzhitov, R., & Brüning, J. C. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2009.08.013 · Cited by 483 · see citing works
Allen, D. L., Cleary, A. S., Speaker, K. J., Lindsay, S. F., Uyenishi, J., Reed, J. M., Madden, M. C., & Mehan, R. S. (2008) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00798.2007 · Cited by 183 · see citing works
Central Leptin Acutely Reverses Diet-Induced Hepatic Insulin Resistance
Pocai, A., Morgan, K., Buettner, C., Gutierrez-Juarez, R., Obici, S., & Rossetti, L. (2005) · Diabetes · doi:10.2337/diabetes.54.11.3182 · Cited by 153 · see citing works
JULLIARD, A., CHAPUT, M., APELBAUM, A., AIME, P., MAHFOUZ, M., & DUCHAMPVIRET, P. (2007) · Behavioural Brain Research · doi:10.1016/j.bbr.2007.05.033 · Cited by 119 · see citing works
Arch, J. R. S. (2008) · Naunyn-Schmiedeberg's Archives of Pharmacology · doi:10.1007/s00210-008-0271-1 · Cited by 96 · see citing works
Estradiol and high fat diet associate with changes in gut microbiota in female ob/ob mice
Acharya, K. D., Gao, X., Bless, E. P., Chen, J., & Tetel, M. J. (2019) · Scientific Reports · doi:10.1038/s41598-019-56723-1 · Cited by 74 · see citing works
Tam, J., Fukumura, D., & Jain, R. K. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2008.11.005 · Cited by 52 · see citing works
Van Den Hoek, A. M., Teusink, B., Voshol, P. J., Havekes, L. M., Romijn, J. A., & Pijl, H. (2008) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2007.01626.x · Cited by 34 · see citing works
- Authors
- Mistry, A. M., Swick, A. G., & Romsos, D. R.
- Affiliations
- Michigan State University (US)
- Pfizer (United States) (US)
- Corresponding author
- Romsos, Dale R.
- Venue
- The Journal of Nutrition
- Publisher
- Elsevier BV
- Published
- 1997-10
- Volume
- 127
- Issue
- 10
- Pages
- 2065-2072
- ISSN
- 0022-3166 (ISSN-L)
- OpenAlex
- W2151083080
- Cited by
- 188
- References
- 35
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 3 · 2023: 1 · 2022: 2 · 2021: 8 · 2020: 4 · 2019: 8 · 2018: 5 · 2017: 2 · 2016: 3 · 2015: 7 · 2014: 8 · 2013: 4 · 2012: 5
- FWCI
- 2.89
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Nutrition (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-15847)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Keywords
- leptin, ob/ob mice, dietary intake, oxygen consumption, metabolic rate, intracerebroventricular administration, hypothalamus, neuropeptide Y, adrenalectomy, glucocorticoids, diet-induced thermogenesis, obesity, appetite regulation
- MeSH terms
- Adrenalectomy, Animals, Dose-Response Relationship, Drug, Eating, Energy Metabolism, Food Deprivation, Injections, Intraventricular, Male, Mice, Obese, Oxygen Consumption, Proteins, Species Specificity, Leptin, Mice
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