Genetic Linkage to Childhood Obesity Saeed Mahmood Mentor: Dr. Akintola Odutola Medical University of theAmericas 3439 Richmond Rd Staten Island,NY 10306 (917) [email protected]
edAbstractHypothesis – Defectin leptin and its receptor gene is linked to childhood obesity because of dysregulationof production of leptin and its receptors. Methods: Articles for this literature review analysis were selected using PubMed, Nature Journals, Oxford Journals, and New England Journal of Medicine. Keywords used to search were “lepr”, “leptin role”, “childhood obesity”, “leptin receptor gene”, “leptin receptor”, “leptin structure”, “leptin receptor structure”, “leptin gene”, and “lepr chromosome”.
Studies used evaluated the role of leptin hormone on childhood obesity. All studies to be relatively recent within a ten-year period. Exclude all studies before 2006 and those not written in English. Focus on studies that involve large number of populations, which includes humans, mice, and animals. All studies to be relatively recent within a ten-year period. Results Several studies reported that the environment, behavior is a major contribute to childhood obesity however there is also a genetic linkage with childhood obesity, specifically defect in leptin hormone or its receptor gene leads to deficiency and dysregulation of leptin hormone and its receptor and it leads to hyperphagia and severe, early-onset obesity. Conclusions Identification of genetic linkage with childhood obesity is a critical issue, because it can help us develop medication to target this problem or even maybe a gene therapy in the future.
Currently there is still lot of research going to necessarily confirm or reject this conclusion that the leptin hormone gene and its receptor gene dysregulation cause childhood obesity. Word count – 240 KeywordsLepr, Lep gene, leptin role, leptin hormone,childhood obesity, leptin receptor gene, leptin receptor, leptin structure,childhood obesity. Introduction Obesity is defined as excess fat mass. Body Mass Index (BMI) is a measurement of the amount of fat person has. Obesity is defined as BMI > 25 kg/m².
Childhood obesity prevenelnece has been increasing. Childhood obesity is linked with numerous health complications and is a major problem in the United States presently. According to the Childhood Obesity Foundation, in 2013 around 43 million infants and children were obese and the numbers are expected to rise.
According to Centers of Disease Control and Prevention childhood obesity affect 12.5 million teens and children in the United States. High BMI leads to cardiovascular dieses (Freedman et al., 2009). Although several socioeconomic factors of various types have been linked causally with childhood obesity, not much is known about genetic linkage of this problem. Childhood obesity mode of inheritance is categorized in two groups either polygenic or monogenic.
In the vast majority of obese children, no syndromal or monogenic cause for the obese state can be diagnosed and therefore a polygenic cause is suggested (Funcke, 2014). Of all monogenic forms of obesity, leptin defeincy caouse by mutation in leptin gene is the only one that is curable (Paz-Filho, 2011). There is some evidence linking defects in several genes (LEP and LEPR genes) responsible for producing leptin and its receptors throughout the body with childhood obesity. The gene defect in LEP gene lead to defect in the protein therefore there is very low amount of hormone in individuals with gene defect (Farooqi, 2014). Several polymorphisms of both leptin and leptin receptor genes were studied in diverse populations for its probable relationship with obesity and the related complications (Khosropur, 2016). Leptin producing gene is located on chromosome 7q31.
3 (Alvarez, 2013). Leptin receptors producing gene is located on chromosome 1.p31.3 (Dias, 2010).
Leptin is a neuroendocrine hormone that is produced and released by adipocyte (Klok, 2007). It increases with amount on adipocytes a an individual as. An obese invidual has a higher amount of leptin produced and realsed by adipocyte compare to lean indivaual given that an obese person has more number of apidyctce. Lepttin with helps control the hunger and increases the energy expindentuure. An increase in leptin has a disadvantage for an obese invidial because it increases the chance of causing a phrmonma known as “leptin resistance”. It circulates in lean individuals at the level of 5 – 15 ng/mL (Khosropour, 2016). Leptin is responsible for regulation of satiety.
leptin stimulates dorsomedial nucleus in the hypthalamus and inhibited lateral nucleus in the hypothalamus. Dorsomedial nucleus is linked with feeding, drinking and circadian rhythm. When the dorsomedial nucleus is stimulated in prevents the intake of the food. The lateral nucleus is also linked with feeding behavior, stimulation of this nucleus leads to intake of the food. In this paper, I will review recent evidence to test my hypothesis that defects in LEPR genes contribute to childhood obesity through mechanism of dysregulation of production of leptin hormone receptors. I chose this topic because it is very important to understand how genetic factors contribute to childhood obesity so as to identify areas where new treatment interventions may be directed in its management. Evidence Table First Author Date of publication Study Design Level of Evidence Study Population Exposure Outcome Results Olza, J.
August 2017 Case-control study 3 Spanish female Children with normal and high BMI. Leptin receptor gene defect Female children with leptin receptor gene variant rs11804081 had higher BMI. Zhao, Y. February 2014 Case control study 3 135 Chinese individual with normal and BMI Missense mutation in exon 3 of leptin gene Gene defect was found in ovbese invidals. Hasnain, Shaban April 2016 Case control 3 475 Pakistani children Leptin gene defect A child with mutation in p. N103K leptin gene had higher BMI than his siblings.
Colmers, W. March 2013 Animal experiment 0 Mouse with pradder-willi syndrome gene Leptin hormone Food intake didn’t not decrease in mouse with PWS gene after an injection with leptin hormone. Hinuy, H. March 2010 Case-control study 3 110 obese and 100 non-obese Individuals. 45 women and 65 men, aged 49 ± 14 years Leptin receptor gene defect Women with defect in leptin gene found to have higher BMI. But not the men. Bahrami, E. May 2014 Case-control study 3 486 adolescents (243 with high and equal number with normal BMI.
Insulin level and leptin levels were high in obese adolescents. Altawil, A. October 2016. Case series 4 Two and healf year old girl with weight gain and hyperhagia Franshit in exon 3 of leptin gene cause the girl to eat more and gain wight Wabitsch, M.
July, 2015. Case series 4 Obese 9 year-old girl, 6 year-old boy with normal weight at birth. Leptin receptor gene Congenital deficiency of leptin gene results in severe early-onset obesity.
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