Insulin and Estrogen Independently and Differentially Reduce Macronutrient Intake in Healthy Men
Open accessAbstract
Context: Insulin administration to the central nervous system inhibits food intake, but this effect has been found to be less pronounced in female compared with male organisms. This sex-specific pattern has been suggested to arise from a modulating influence of estrogen signaling on the insulin effect. Objective: We assessed in healthy young men whether pretreatment with transdermal estradiol interacts with the hypophagic effect of central nervous insulin administration via the intranasal pathway. Design, Setting, Participants, and Intervention: According to a 2×2 design, two groups of men (n = 16 in each group) received a 3-day transdermal estradiol (100 µg/24 h) or placebo pretreatment and on two separate mornings were intranasally administered 160 IU regular human insulin or placebo. Main Outcome Measures: We assessed free-choice ad libitum calorie intake from a rich breakfast buffet and relevant blood parameters in samples collected before and after breakfast. Results: Estrogen treatment induced a 3.5-fold increase in serum estradiol concentrations and suppressed serum testosterone concentrations by 70%. Independent of estradiol administration, intranasal insulin reduced the intake of carbohydrates during breakfast, attenuating in particular the consumption of sweet, palatable foods. Estradiol treatment per se decreased protein consumption. We did not find indicators of eating-related interactions between both hormones. Conclusions: Results indicate that, in an acute setting, estrogen does not interact with central nervous insulin signaling in the control of eating behavior in healthy men. Insulin and estradiol rather exert independent inhibiting effects on macronutrient intake.
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In healthy men, estrogen administration did not alter the response in eating behaviour after administration of nasal insulin.
“This is contrary to findings in healthy men, where estrogen administration did not alter the response in eating behaviour after administration of nasal insulin36.”
From Brain insulin action on peripheral insulin sensitivity in women depends on menstrual cycle phase (2023) · cites this paper as [36]
Pretreating healthy young men with transdermal oestrogen for three consecutive days, leading to a 3.5-fold increase in serum oestradiol, did not attenuate the suppression in calorie consumption triggered by IN insulin.
“pretreating healthy young men with transdermal oestrogen for three consecutive days, which led to a 3.5-fold increase in their serum oestradiol concentrations, did not attenuate the suppression in calorie consumption triggered by IN insulin.”
From Intranasal insulin (2021) · cites this paper as [47]
Delivery schedules synced to food intake might be necessary for the catabolic impact of IN insulin to emerge.
“suggesting that delivery schedules synced to food intake 39,42,44,47 might be necessary for the catabolic impact of IN insulin to emerge.”
From Intranasal insulin (2021) · cites this paper as [47]
Cites
Sniffing neuropeptides: A transnasal approach to the human brain
Born, J., Lange, T., Kern, W., McGregor, G. P., Bickel, U., & Fehm, H. L. (2002) · Nature Neuroscience · doi:10.1038/nn0602-849 · Cited by 1,356 · see citing works
The role of estrogens in control of energy balance and glucose homeostasis
Mauvais-Jarvis, F., Clegg, D. J., & Hevener, A. L. (2013) · Endocrine Reviews · doi:10.1210/er.2012-1055 · Cited by 1,329 · see citing works
Chronic intracerebroventricular infusion of insulin reduces food intake and body weight of baboons
Woods, S. C., Lotter, E. C., McKay, L. D., & Porte, D. (1979) · Nature · doi:10.1038/282503a0 · Cited by 1,114 · see citing works
Distinct Hypothalamic Neurons Mediate Estrogenic Effects on Energy Homeostasis and Reproduction
Xu, Y., Nedungadi, T. P., Zhu, L., Sobhani, N., Irani, B. G., Davis, K. E., Zhang, X., Zou, F., Gent, L. M., Hahner, L. D., et al. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.08.009 · Cited by 597 · see citing works
Gonadal Hormones Determine Sensitivity to Central Leptin and Insulin
Clegg, D. J., Brown, L. M., Woods, S. C., & Benoit, S. C. (2006) · Diabetes · doi:10.2337/diabetes.55.04.06.db05-1339 · Cited by 552 · see citing works
Modulation of appetite by gonadal steroid hormones
Asarian, L., & Geary, N. (2006) · Philosophical Transactions of the Royal Society B: Biological Sciences · doi:10.1098/rstb.2006.1860 · Cited by 506 · see citing works
Asarian, L., & Geary, N. (2002) · Hormones and Behavior · doi:10.1006/hbeh.2002.1835 · Cited by 336 · see citing works
Differential Sensitivity to Central Leptin and Insulin in Male and Female Rats
Clegg, D. J., Riedy, C. A., Smith, K. A. B., Benoit, S. C., & Woods, S. C. (2003) · Diabetes · doi:10.2337/diabetes.52.3.682 · Cited by 332 · see citing works
Targeted estrogen delivery reverses the metabolic syndrome
Finan, B., Yang, B. S., Ottaway, N., Stemmer, K., Müller, T. D., Yi, C., Habegger, K. M., Schriever, S. C., García‐Cáceres, C., Kabra, D. G., et al. (2012) · Nature Medicine · doi:10.1038/nm.3009 · Cited by 330 · see citing works
Menstrual cycle and appetite control: implications for weight regulation
Dye, L., & Blundell, J. E. (1997) · Human Reproduction · doi:10.1093/humrep/12.6.1142 · Cited by 304 · see citing works
Benedict, C., Kern, W., Schultes, B., Born, J., & Hallschmid, M. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2007-2606 · Cited by 296 · see citing works
Gut-Brain Cross-Talk in Metabolic Control
Clemmensen, C., Müller, T. D., Woods, S. C., Berthoud, H., Seeley, R. J., & Tschöp, M. H. (2017) · Cell · doi:10.1016/j.cell.2017.01.025 · Cited by 296 · see citing works
Stouffer, M. A., Woods, C. A., Patel, J. C., Lee, C. R., Witkovsky, P., Bao, L., Machold, R. P., Jones, K. T., de Vaca, S. C., Reith, M. E. A., et al. (2015) · Nature Communications · doi:10.1038/ncomms9543 · Cited by 286 · see citing works
Intranasal Insulin Reduces Body Fat in Men but not in Women
Hallschmid, M., Benedict, C., Schultes, B., Fehm, H.-L., Born, J., & Kern, W. (2004) · Diabetes · doi:10.2337/diabetes.53.11.3024 · Cited by 281 · see citing works
Self-citationCross-talk between estrogen and leptin signaling in the hypothalamus
Gao, Q., & Horváth, T. L. (2008) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00733.2007 · Cited by 249 · see citing works
Insulin induces long-term depression of ventral tegmental area dopamine neurons via endocannabinoids
Labouèbe, G., Liu, S., Dias, C., Zou, H., Wong, J. C. Y., Karunakaran, S., Clee, S. M., Phillips, A. G., Boutrel, B., & Borgland, S. L. (2013) · Nature Neuroscience · doi:10.1038/nn.3321 · Cited by 239 · see citing works
Oxytocin Reduces Reward-Driven Food Intake in Humans
Ott, V., Finlayson, G., Lehnert, H., Heitmann, B., Heinrichs, M., Born, J., & Hallschmid, M. (2013) · Diabetes · doi:10.2337/db13-0663 · Cited by 226 · see citing works
Self-citationMebel, D. M., Wong, J. C. Y., Dong, Y., & Borgland, S. L. (2012) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2012.08168.x · Cited by 215 · see citing works
Control of energy homeostasis by insulin and leptin: Targeting the arcuate nucleus and beyond
Könner, A. C., Klöckener, T., & Brüning, J. C. (2009) · Physiology & Behavior · doi:10.1016/j.physbeh.2009.03.027 · Cited by 215 · see citing works
Vogt, M. C., & Brüning, J. C. (2012) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2012.11.004 · Cited by 188 · see citing works
Hallschmid, M., Higgs, S., Thienel, M., Ott, V., & Lehnert, H. (2012) · Diabetes · doi:10.2337/db11-1390 · Cited by 181 · see citing works
Self-citationIntraventricular insulin and leptin reduce food intake and body weight in C57BL/6J mice
Brown, L. M., Clegg, D. J., Benoit, S. C., & Woods, S. C. (2006) · Physiology & Behavior · doi:10.1016/j.physbeh.2006.08.008 · Cited by 139 · see citing works
Reduction of food intake in the ovulatory phase of the menstrual cycle
Lyons, P., Truswell, A. S., Mira, M., Vizzard, J., & Abraham, S. F. (1989) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/49.6.1164 · Cited by 138 · see citing works
Benedict, C., Brede, S., Schiöth, H. B., Lehnert, H., Schultes, B., Born, J., & Hallschmid, M. (2011) · Diabetes · doi:10.2337/db10-0329 · Cited by 129 · see citing works
Self-citationGorczyca, A. M., Sjaarda, L. A., Mitchell, E. M., Perkins, N. J., Schliep, K. C., Wactawski‐Wende, J., & Mumford, S. L. (2015) · European Journal of Nutrition · doi:10.1007/s00394-015-0931-0 · Cited by 125 · see citing works
Estrogen receptor‐α distribution in the human hypothalamus in relation to sex and endocrine status
Kruijver, F. P. M., Balesar, R. A., Espila, A. M., Unmehopa, U. A., & Swaab, D. F. (2002) · The Journal of Comparative Neurology · doi:10.1002/cne.10416 · Cited by 124 · see citing works
Thammacharoen, S., Lutz, T. A., Geary, N., & Asarian, L. (2007) · Endocrinology · doi:10.1210/en.2007-0340 · Cited by 121 · see citing works
Variations in food preference and consumption across the menstrual cycle
Bowen, D. J., & Grunberg, N. E. (1990) · Physiology & Behavior · doi:10.1016/0031-9384(90)90144-s · Cited by 120 · see citing works
Stout, M. B., Steyn, F. J., Jurczak, M. J., Camporez, J.-P. G., Zhu, Y., Hawse, J. R., Jurk, D., Palmer, A. K., Xu, M., Pirtskhalava, T., et al. (2017) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/glv309 · Cited by 119 · see citing works
Figlewicz, D. P., Bennett, J. L., Aliakbari, S., Zavosh, A., & Sipols, A. J. (2008) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.90334.2008 · Cited by 115 · see citing works
Central insulin modulates food valuation via mesolimbic pathways
Tiedemann, L. J., Schmid, S. M., Hettel, J., Giesen, K., Francke, P., Büchel, C., & Brassen, S. (2017) · Nature Communications · doi:10.1038/ncomms16052 · Cited by 113 · see citing works
Intraventricular insulin and the level of maintained body weight in rats.
Chavez, M., Kaiyala, K. J., Madden, L. J., Schwartz, M. W., & Woods, S. C. (1995) · Behavioral Neuroscience · doi:10.1037//0735-7044.109.3.528 · Cited by 111 · see citing works
Estrogen receptor β expression in the mouse forebrain: Age and sex differences
Zuloaga, D. G., Zuloaga, K. L., Hinds, L. R., Carbone, D. L., & Handa, R. J. (2013) · The Journal of Comparative Neurology · doi:10.1002/cne.23400 · Cited by 109 · see citing works
Ovarian hormone fluctuations predict within-cycle shifts in women's food intake
Roney, J. R., & Simmons, Z. L. (2017) · Hormones and Behavior · doi:10.1016/j.yhbeh.2017.01.009 · Cited by 107 · see citing works
Intraventricular insulin and the level of maintained body weight in rats.
Chavez, M., Kaiyala, K. J., Madden, L. J., et al. (1995) · Behavioral Neuroscience · doi:10.1037/0735-7044.109.3.528 · Cited by 96 · see citing works
Krug, R., Benedict, C., Jan Born, A., & Hallschmid, M. (2010) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2010-0744 · Cited by 74 · see citing works
Self-citationCentral insulin and macronutrient intake in the rat
Chavez, M., Riedy, C. A., van Dijk, G., & Woods, S. C. (1996) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1996.271.3.r727 · Cited by 68 · see citing works
Estradiol is a critical regulator of food-reward behavior.
Richard, J. E., López-Ferreras, L., Anderberg, R., Olandersson, K., & Skibicka, K. (2017) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2017.01.014 · Cited by 66 · see citing works
Androgen (dihydrotestosterone)–mediated regulation of food intake and obesity in female mice
Kanaya, N., Vonderfecht, S. L., & Chen, S. (2013) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2013.04.001 · Cited by 38 · see citing works
Central effects of testosterone on food intake in male rats
Núñez, A. A., Siegel, L. I., & Wade, G. N. (1980) · Physiology & Behavior · doi:10.1016/0031-9384(80)90238-3 · Cited by 33 · see citing works
Santiago, J. C. P., & Hallschmid, M. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00054 · Cited by 18 · see citing works
Self-citationMetabolic Impact Of Sex Hormones On Obesity
Brown, L. M., Gent, L., Davis, K. E., & Clegg, D. J. (2010) · Brain Research · doi:10.1016/j.brainres.2010.04.056 · Cited by 13 · see citing works
Dietary and Hypothalamic Changes in Δ 4-Androstenedione-Treated Zucker Rats
Hargrave, K. R., Wright, B. E., Svec, F., & Porter, J. R. (1997) · Physiology & Behavior · doi:10.1016/s0031-9384(96)00514-8 · Cited by 10 · see citing works
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Nijssen, K. M. R., Mensink, R. P., & Joris, P. J. (2022) · Neuroendocrinology · doi:10.1159/000526717 · Cited by 37 · see citing works
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- Authors
- Krug, R., Mohwinkel, L., Drotleff, B., Born, J., & Hallschmid, M.
- Affiliations
- University of Tübingen (DE)
- University of Lübeck (DE)
- Department of Medical Psychology and Behavioral Neurobiology, University of Tübingen, Tübingen, Germany
- Helmholtz Munich (DE)
- Corresponding author
- Hallschmid, Manfred
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2018-01-12
- Volume
- 103
- Issue
- 4
- Pages
- 1393-1401
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2783864434
- Cited by
- 16
- References
- 42
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 3 · 2023: 2 · 2022: 3 · 2021: 2 · 2020: 2 · 2019: 1
- FWCI
- 0.70
- Type
- journal article
- Language
- en
- Open access
- Licence
- other-oa
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Site cant be reached (submittedVersion, other-oa)
- PuSH - Publication Server of Helmholtz Zentrum München (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Social Sciences › Psychology › Clinical Psychology › Eating Disorders and Behaviors
- Keywords
- insulin, estradiol, macronutrient intake, food intake regulation, intranasal insulin, transdermal estradiol, sex differences, testosterone, carbohydrate intake, protein intake, dietary habits, healthy men
- MeSH terms
- Administration, Intranasal, Adolescent, Adult, Blood Glucose, Energy Intake, Dietary Carbohydrates, Drug Interactions, Eating, Estradiol, Feeding Behavior, Humans, Insulin, Male, Psychometrics, Random Allocation, Testosterone, Young Adult, Transdermal Patch
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