Genetic Linkage to Childhood Obesity
Mentor: Dr. Akintola Odutola
Medical University of the
3439 Richmond Rd Staten Island,
Hypothesis – Defect
in leptin and its receptor gene is linked to childhood obesity because of dysregulation
of production of leptin and its receptors.
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.
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.
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
Lepr, Lep gene, leptin role, leptin hormone,
childhood obesity, leptin receptor gene, leptin receptor, leptin structure,
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).
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
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
Date of publication
Level of Evidence
Spanish female Children with normal and high
Leptin receptor gene defect
Female children with leptin receptor gene
variant rs11804081 had higher BMI.
135 Chinese individual with normal and BMI
Missense mutation in exon 3 of leptin gene
Gene defect was found in ovbese invidals.
475 Pakistani children
Leptin gene defect
A child with mutation in p. N103K leptin
gene had higher BMI than his siblings.
Mouse with pradder-willi syndrome gene
intake didn’t not decrease in mouse with PWS gene after an injection with
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.
486 adolescents (243 with high and equal
number with normal BMI.
Insulin level and leptin levels were high in
Two and healf year old girl with weight gain
Franshit in exon 3 of leptin gene cause the
girl to eat more and gain wight
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.
Reteive from Marie Pigeyre, Fereshteh T. Yazdi, Yuvreet Kaur, David Meyre.
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