Here we discussed few details about leptin and it's effect on obesity.

1. Presented by
Vicktor Ghosh and Sunipa Maity
Registration no:- 181240210105 and 181240210093
Roll No:- 12401918011 and 12401918023
Under the guidance of
Dr. Rana Datta
Assistant Professor
Gupta College of Technological Sciences

2. OBESITY
 Obesity is a condition in which excess body fat has accumulated to
such an extent that it may have a negative effect on health.
 Indicated by body mass index [BMI] and ≥30 kg/m² is defind as
obesity.
ETIOLOGY
• Excessive food energy intake and a lack of physical
activity as the cause of most cases of obesity.
• Genetics, medical reasons, or psychiatric illness.

3. LEPTIN AND IT’S RECEPTORS
 OBR is a type I cytokine receptor and it has a several short isomers
(ObRa, ObRc, ObRd, and ObRf) and one long isomer (ObRb). Among
them ObRb is the main isoform responsible for the effect of leptin on
body weight control.
 After leptin binds to ObRb it gets activated and triggers various
transduction pathways which causes lowering of body weight, such as
follows-
a. Activation of the Janus tyrosine kinase 2 (JAK2)/signal transducer and
activator of transcription 3 (STAT3) pathway →increase of
anorexigenic signals.
b. Activation of the insulin receptor substrate
(IRS)/phosphatidylinositide 3-kinase (PI3K) pathway, essential for the
regulation of glucose homeostasis.
c. Leptin inhibits the energy sensor adenosine monophosphate activated
protein kinase (AMPK) in the brain to decrease eating.
d. Activation of extracellular signal regulated kinase (ERK) causes
anorectic action.
Fig:- Mechanism of Leptin

4. LEPTIN EXPRESSION ON OBESITY
•Plasma leptin levels and ob mRNA content decrease in
individuals with obesity at the initial time of weight loss but
increases as they continue to lose weight.
•Suppressor of cytokine signalling 3 (SOCS3) expression
induce ceramide synthesis which causes leptin resistance and
a high fat diet may cause SOCS3 expression.
• Studies confirmed that Ob gene has few polymorphs and
Lep-R is one of them and it is identified in the 5’-untranslated
region of the leptin gene.
•A distant leptin enhancer 1 (LE1) and leptin regulatory
element 1 (LepRE1) is essential for fat regulated expression.
Fig:- Leptin expression

5. MECHANISMS UNDERPINNING LEPTIN RESISTANCE
•Reduction in leptin access to CNS.
•Impairment of leptin signalling in
hypothalamic neurons.
•Impairment of MC4R downstream signal
transduction in neural circuits.
•Hypothalamic ER stress in central leptin
resistance.
•Defective autophagy as a contributor of
leptin resistance.
Fig:- Mechanism of leptin resistance

6. STRATEGIES TO OVERCOME LEPTIN RESISTANCE
 Caloric restriction and exercise.
 Inhibition of SOCS3 and PTP1B.
 POMC neuron activation.
 Increase in leptin receptor expression and cell surface localization.
TREATMENT OF OBESITY BASED ON LEPTIN
• Excessive Leptin analogous:- Metreleptin is a once daily subcutaneously
administered leptin analogue approved by the FDA in 2014 for use in people with
leptin deficiency or congenital/acquired lipodystrophy.
•Phentermine and topiramate combination therapy:- Phentermine plus topiramate
(TPM) in combination markedly decreased body weight in overweight and obese
patients.

7. CONCLUSION
Increase prevalence of obesity in the world now a days is an actual health
issue. An advance of science in revealing mystery on mechanism of leptin
resistance is very useful to provide a new molecule target for anti obesity
agent.
REFERENCES
[1] M. Wauters, RV. Considine, LF. Van Gaal, Human leptin from an adipocyte hormone to an endocrine mediator, Eu Endocrinol. 143 (2000)
293-311
[2] Lee GH. Proenca R, Montez JM. Carroll KM, Darvishzadeh JG, Lee II, et al. Abnormal splicing of the leptin receptordiabetic mice. Nature
(1996) 379(6566) 632-5. doi:10.1038/379632013.
[3] Bates SH, Stearns WH, Dundon TA, Schubert M.Tso AWK, Wang Y, et al. STAT3 signalling is required for leptin regulatof energy balance
but not reproduction. Nature (2003) 421 (6925)-856-9. doi:10.1038/nature01388141.
[4] Morton Gl. Gelling RW. Niswender KD, Morrison CD, Rhodes C), Schwartz MW. Leptin regulates insulin sensitivity phosphatidylinositol-
3-OH kinase signaling in mediobasal hypothalamic neurons Cell Metab (2005) 2(6)-411 doldot:10.1016/j.cmet.2005.10.009
[5] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4195360/
[6] https://www.sciencedirect.com/science/article/abs/pii/S0306987716300494
[7] https://www.nature.com/articles/s41573-021-00337-8.pdf
[8] https://www.embopress.org/doi/full/10.1002/emmm.201303227