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Table of Contents
Year : 2012  |  Volume : 16  |  Issue : 9  |  Page : 532-533

Metformin; A character actor in the leptin story!

1 Department of Endocrinology, Consultant Endocrinologist, Excel Center (A Unit of Excelcare Hospitals), Guwahati, Asssam, India
2 Department of Endocrinology, Bharti Hospitals and BRIDE, Karnal, Haryana, India
3 Department of Endocrinology, Regional Institute of Medical Sciences, Imphal, Manipur, India

Date of Web Publication4-Jan-2013

Correspondence Address:
Manash P Baruah
Consultant Endocrinologist, Excel Center (A Unit of Excelcare Hospitals), Barthakur Mill Road, Ulubari, Guwahati - 781 007, Asssam
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2230-8210.105569

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How to cite this article:
Baruah MP, Kalra S, Ranabir S. Metformin; A character actor in the leptin story!. Indian J Endocr Metab 2012;16, Suppl S3:532-3

How to cite this URL:
Baruah MP, Kalra S, Ranabir S. Metformin; A character actor in the leptin story!. Indian J Endocr Metab [serial online] 2012 [cited 2020 Jun 6];16, Suppl S3:532-3. Available from: http://www.ijem.in/text.asp?2012/16/9/532/105569

Our current understanding of metabolic processes tells us that there is more to the control of eating behavior then mere stimulation by hunger and hedonic sensation. How brain in general and hypothalamus in particular interacts with peripheral tissue to control feeding has remained a subject of intensive scientific discussions. Lessons learnt from rare but distinctive mongentic disorders causing extreme obesity have turned the spotlight on hypothalamo-leptin-melanocortin system. And that is how the leptin story began, taking other factors along in its course. [1] Metformin, a biguanide, has been as a first line drug of choice along with lifestyle intervention in the management of type 2 diabetic patients. It seems this molecule has been assigned to play the role of a protagonist in the story of management of T2DM. This superstar status won by a drug discovered half a century ago by Professor Jeanne Sterne is though extraordinary, did not come without struggle. To quote Professor Gerald Slama and Professor Ian Campbell, two pioneers who worked on this molecule extensively through the recent decades, "The metformin journey is one of the discovery, dismissal and re-discovery and its very survival is due to some defining moments over the past 50 years." [2]

How do we combine these two interesting stories. Do we have a substantial plot to find this wonderful molecule playing an important character role in modifying defect(s) in the leptin actions.

Metformin induced reduction in leptin level in morbidly obese individuals has been proven in several studies, but some others have shown evidence to the contrary. [3],[4],[5],[6] Possible explanations for these discrepancies may be the length of treatment and the study population, with obese people showing a decrease in leptin levels after long-term treatment. On metformin, there were linear trends in decrements in weight, girth, waist circumference, waist/hip ratio, insulin, and leptin. Reduction in leptin paralleled the reduction in insulin levels and somewhat greater in those with higher baseline serum leptin. [3] Interestingly, distinct reduction in serum leptin level was observed in non obese healthy individual on metformin, without any reduction in body weight. [4] Hence, the scientific community is trying to look beyond changes in adipocyte morphology in trying to define the role of metformin in leptin biology. [7] More recently, it has been demonstrated that weight loss achieved by metformin was correlated with pretreatment plasma leptin levels. This effect of metformin was paralleled by a stimulation of the expression of the leptin receptor gene (ObRb) in the arcuate nucleus, thus identifying the hypothalamic ObRb as a gene modulated after metformin treatment. [8] It has suggested that the anorectic effects of metformin are potentially mediated via an increase in the central sensitivity to leptin.

Thus, the time is just right and ripe to assign another pioneering role, at least of a character actor, if not the protagonist, for metformin in the story of leptin biology. As scientists travel to the deeper realms of the subject and write and rewrite the story for the medical community at large, the people involved in the editorial task of this issue will continue to derive satisfaction of not missing it out, and of course doing a job on-time.

   References Top

1.Ranadive SA, Vaisse Christian V. lessons from Extreme Human Obesity: Monogenic Disrorders. In: Karnieli E, Leroith D, editors. Endocrinol Metab Clin N Am 2008;37:733-51.  Back to cited text no. 1
2.Slama G, Cambell IW. Preface. In: Bailey CJ, Cambell IW, Chan JC, Davidson JA, Howlett HCS, Ritz P, editors. Metformin. UK: Willy Chichester; 2007. p. 7-8.  Back to cited text no. 2
3.Glueck CJ, Fontaine RN, Wang P, Subbiah MT, Weber K, Illig E, et al. Metformin reduces weight, centripetal obesity, insulin, leptin, and low-density lipoprotein cholesterol in nondiabetic, morbidly obese subjects with body mass index greater than 30. Metabolism 2001;50:856-61.  Back to cited text no. 3
4.Fruehwald-Schultes B, Oltmanns KM, Toschek B, Sopke S, Kern W, Born KJ, et al. Short-term treatment with metformin decreasess erumleptin concentration without affecting body weight and body fat content in normal-weight healthy men. Metabolism 2002;51:531-6.   Back to cited text no. 4
5.Guler S, Cakir B, Demirbas B, Gursoy G, Serter R, Aral Y. Leptin concentrations are related to glycaemic control, but do not change with short-term oral anti diabetic therapy in female patientswith type 2 diabetes mellitus. Diabetes Obes Metab 2000;2:313-6.  Back to cited text no. 5
6.Adamia N, Virsaladze D, Charkviani N, Skhirtladze M, Khutsishvili M. Effect of metformin therapy on plasma adiponectin and leptin levels in obese and insulin resistant postmenopausal females with type 2 diabetes. Georgian Med News 2007;145:52-5.  Back to cited text no. 6
7.Klein J, Westphal S, Kraus D, Meier B, Perwitz N, Ott V, et al. Metformin inhibits leptin secretion via a mitogen-activated proteinkinase signalling pathway in brown adipocytes. J Endocrinol 2004;183:299-307.  Back to cited text no. 7
8.Aubert G, Mansuy V, Voirol MJ, Pellerin L, Pralong FP. The anorexigenic effects of metformin involve increases in hypothalamic leptin receptor expression. Metabolism 2011;60:327-34  Back to cited text no. 8

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