EFFECT OF KETOGENIC DIET ON LEPTIN LEVEL IN A DEPRESSED RAT MODEL

Authors

  • Amber Farid Jinnah Medical College, Peshawar, Pakistan
  • Muhammad Omar Malik Khyber Medical University, Peshawar, Pakistan
  • Syed Murtaza Shah Bukhari khyber medical university
  • Saadia Anwar Jinnah Medical College, Peshawar, Pakistan
  • Muhammad Irfan Shereen Muhammad College Of Medicine, Peshawar, Pakistan.
  • Abdu Haseeb Muhammad College Of Medicine, Peshawar, Pakistan.
  • Awais ul Islam Maqsood Medical Center, Peshawar, Pakistan.
  • Saif ul Islam Jinnah Medical College, Peshawar, Pakistan
  • Muhammad Mustafa Muhammad College Of Medicine, Peshawar, Pakistan.
  • Muhammad Mobashar The University of Agriculture, Peshawar, Pakistan

DOI:

https://doi.org/10.69656/pjp.v22i1.1924

Keywords:

Depression, Forced swim test, Intra-cardiac puncture, Ketogenic diet, Ketosis, Leptin, Preference test, Sucrose re-strainer

Abstract

Background: Depression is multidimensional disorder involving neuroendocrine disturbances. Several hormones are affected in depression, including gut related hormones such as leptin. Decreased leptin levels have been associated with worsening depressive symptoms and altered satiety. This study aimed to evaluate effect of ketogenic diet on leptin levels in rat model and its impact on depressive behaviour. Methods: This study included male Sprague Dawley rats (n=39) randomly divided into three equal groups (n=13/group) and housed at Khyber Medical University. Depression was induced using chronic restraint stress model by restraining rats for two hours daily for 21 days. Depression was confirmed using Forced Swim Test and Sucrose Preference Test. Group A served as depressed control group and was sacrificed after confirmation of depression. Group B received normal diet for four weeks, while Group C was administered ketogenic diet for four weeks. Ketosis was confirmed before sacrifice. Blood samples were collected through intra-cardiac puncture, centrifuged, and stored at ?80 °C. Serum leptin levels were measured using ELISA. Behavioural tests were repeated to assess effect of dietary intervention. Results: Mean leptin levels were 0.92±0.47 in depressed control group and increased to 1.32±0.33 in ketogenic dietgroup (p=0.019). Forced Swim Test mobility significantly increased (p=0.001), while Sucrose Preference Test scores significantly improved (p=0.026) in ketogenic diet-treated depressed group. Conclusion: A four week ketogenic diet increased leptin levels and improved depressive behaviour in depressed rats.

Pak J Physiol 2026:22(1):37–41, DOI: https://doi.org/10.69656/pjp.v22i1.1924

Downloads

Download data is not yet available.

Author Biographies

Amber Farid, Jinnah Medical College, Peshawar, Pakistan

Department of Physiology,

Phd Scholar

Muhammad Omar Malik, Khyber Medical University, Peshawar, Pakistan

Professor.

 Institute of Basic Medical Sciences

Saadia Anwar, Jinnah Medical College, Peshawar, Pakistan

Assistant professor,

Department of Physiology

Muhammad Irfan Shereen, Muhammad College Of Medicine, Peshawar, Pakistan.

Assistant professor,

Department of Physiology

Abdu Haseeb, Muhammad College Of Medicine, Peshawar, Pakistan.

lecturer,

Department of Physiology

Awais ul Islam, Maqsood Medical Center, Peshawar, Pakistan.

House Officer, Intern in Internal Medicine.

Saif ul Islam, Jinnah Medical College, Peshawar, Pakistan

MBBS Student.

Muhammad Mustafa, Muhammad College Of Medicine, Peshawar, Pakistan.

lecturer.

Department of Physiology.

Muhammad Mobashar, The University of Agriculture, Peshawar, Pakistan

Assistant professor.

Faculty of Animal Husbandry and Veterinary Sciences.

References

Fox ME, Lobo MK. The molecular and cellular mechanisms of depression: a focus on reward circuitry. Mol Psychiatry 2019;24(12):1798–815.

Moreno X, Gajardo J, Monsalves MJ. Gender differences in positive screen for depression and diagnosis among older adults in Chile. BMC Geriatr 2022;22(1):54.

Zhang Y, Zhang J, Li H, Jiang Y. The relationship between socioeconomic status and depression: a systematic review and meta-analysis. Adv Psychol Sci 2022;30(12):2650.

Bedaso A, Mekonnen N, Duko B. Estimate of the prevalence of depression among older people in Africa: a systematic review and meta-analysis. Aging Ment Health 2022;26(6):1095–105.

Paoli C, Misztak P, Mazzini G, Musazzi L. DNA methylation in depression and depressive-like phenotype: biomarker or target of pharmacological intervention? Curr Neuropharmacol 2022;20(12):2267–91.

Deng SL, Chen JG, Wang F. Microglia: a central player in depression. Curr Med Sci 2020;40(3):391–400.

Shorey S, Ng ED, Wong CHJ. Global prevalence of depression and elevated depressive symptoms among adolescents: A systematic review and meta?analysis. Br J Clin Psychol 2022;61(2):287–305.

Kawaharada R, Sugimoto T, Uchida K, Murata S, Tsuboi Y, Isa T, et al. Indirect effects of social activity on appetite via depressive symptoms in community-dwelling older adults: a cross-sectional study. Appetite 2022;168:105705.

Tasci G, Kaya S, Kalayci M, Atmaca M. Increased ghrelin and decreased leptin levels in patients with antisocial personality disorder. J Affect Disord 2022;317:22–8.

Morshedzadeh N, Ahmadi AR, Tahmasebi R, Tavasolian R, Heshmati J, Rahimlou M. Impact of low-carbohydrate diet on serum levels of leptin and adiponectin levels: a systematic review and meta-analysis in adult. J Diabetes Metab Disord 2022;21(1):979–90.

Eikelis N, Esler M, Barton D, Dawood T, Wiesner G, Lambert G. Reduced brain leptin in patients with major depressive disorder and in suicide victims. Mol Psychiatry 2006;11(9):800–1.

Jow GM, Yang TT, Chen CL. Leptin and cholesterol levels are low in major depressive disorder, but high in schizophrenia. J Affect Disord 2006;90(1):21–7.

Kraus T, Haack M, Schuld A, Hinze-Selch D, Pollmächer T. Low leptin levels but Normal body mass indices in patients with depression or schizophrenia. Neuroendocrinology 2001;73(4):243–7.

Yang K, Xie G, Zhang Z, Wang C, Li W, Zhou W, et al. Levels of serum interleukin (IL)-6, IL-1?, tumour necrosis factor-? and leptin and their correlation in depression. Aust NZ J Psychiatry 2007;41(3):266–73.

Morris AA, Ahmed Y, Stoyanova N, Hooper WC, De Staerke C, Gibbons G, et al. The association between depression and leptin is mediated by adiposity. Psychosom Med 2012;74(5):483–8.

Tian H, Hu Z, Xu J, Wang C. The molecular pathophysiology of depression and the new therapeutics. Med Comm 2022;3(3):e156.

Kendall K, Van Assche E, Andlauer TFM, Choi K, Luykx JJ, Schulte EC, et al. The genetic basis of major depression. Psychol Med 2021;51(13):2217–30.

Picó C, Palou M, Pomar CA, Rodríguez AM, Palou A. Leptin as a key regulator of the adipose organ. Rev Endocr Metab Disord 2022;23(1):13–30.

Mela V, Samur NS, Vijaya AK, Gálvez VJ, García-Martín ML, Bandera B, et al. Ketogenic diet is less effective in ameliorating depression and anxiety in obesity than Mediterranean diet: A pilot study for exploring the GUT-brain axis. Brain, Behavior, and Immunity 2025:106167.

Mentzelou M, Dakanalis A, Vasios GK, Gialeli M, Papadopoulou SK, Giaginis C. The relationship of ketogenic diet with neurodegenerative and psychiatric diseases: a scoping review from basic research to clinical practice. Nutrients 2023;15(10):2270.

Zou X, Zhong L, Zhu C, Zhao H, Zhao F, Cui R, et al. Role of leptin in mood disorder and neurodegenerative disease. Frontiers in Neuroscience 2019;13:378.

Ge T, Fan J, Yang W, Cui R, Li B. Leptin in depression: a potential therapeutic target. Cell Death Dis 2018;9(11):1096.

Chyra M, Swietochowska E, Gorska-Flak K, Dudzinska M, Oswiecimska J. The effect of the ketogenic diet on leptin, chemerin and resistin levels in children with epilepsy. Neuro Endocrinol Lett 2021;42(7):489–99.

Park S, Kim DS, Kang S, Daily JW 3rd. A ketogenic diet impairs energy and glucose homeostasis by the attenuation of hypothalamic leptin signaling and hepatic insulin signaling in a rat model of non-obese type 2 diabetes. Exp Biol Med 2011;236(2):194–204.

Mao Y, Xu Y, Yuan X. Validity of chronic restraint stress for modeling anhedonic-like behavior in rodents: a systematic review and meta-analysis. J Int Med Res 2022;50(2):03000605221075816.

Ha GE, Cheong E. Chronic restraint stress decreases the excitability of hypothalamic POMC neuron and increases food intake. Exp Neurobiol 2021;30(6):375–86.

Yankelevitch-Yahav R, Franko M, Huly A, Doron R. The forced swim test as a model of depressive-like behavior. J Vis Exp 2015;(97):52587.

Brandwein C, Leenaars CH, Becker L, Pfeiffer N, Iorgu AM, Hahn M, et al. A systematic mapping review of the evolution of the rat Forced Swim Test: Protocols and outcome parameters. Pharmacol Res 2023;196:106917.

Primo MJ, Fonseca-Rodrigues D, Almeida A, Teixeira PM, Pinto-Ribeiro F. Sucrose preference test: A systematic review of protocols for the assessment of anhedonia in rodents. Eur Neuropsychopharmacol 2023;77:80–92.

Downloads

Published

31-03-2026

How to Cite

1.
Amber Farid, Muhammad Omar Malik, Bukhari SMS, Saadia Anwar, Muhammad Irfan Shereen, Abdul Haseeb, et al. EFFECT OF KETOGENIC DIET ON LEPTIN LEVEL IN A DEPRESSED RAT MODEL. Pak J Phsyiol [Internet]. 2026 Mar. 31 [cited 2026 Apr. 10];22(1):37-41. Available from: https://pjp.pps.org.pk/index.php/PJP/article/view/1924