**2. Leptin**

The discovery of leptin 15 years ago generated great excitement that the treatment for obesity had been found, and thus, this prototypical adipocyte-secreted protein/ cytokine was named leptin after the Greek word "leptos" for thin. Leptin is a group of 167 amino acids in human leptin gene mainly made up of adipose tissue and enterocytes which mainly regulate energy balance by inhibiting hunger. It is released by white adipose tissue and leptin level is key indicator of body fat. As like other hormones leptin is secreted at regular temporal pattern i.e. highest secretion in early morning and evening. Leptin mainly is an indicator of how much energy stored in fats and caloric intake [5].

### **2.1 Types of leptin receptors**


### **2.2 Mechanism of action of leptin**

Leptin (Greek word leptos– thin) also known as "Ob gene" that is located on chromosome number 7. Main role of leptin is to achieve an energy balance in the body. Leptin binds to receptors in brain and performs several actions that may prove that leptin is important in treating obesity**.**

It works through two distinct types of neurons in arcuate nucleus of hypothalamus.

1.POMC/CART (Pro-opiomelanocortin/cocaine and amphetamine regulated transcripts) neurons

**Figure 1.** *Mechanism of action of leptin.*

2.NPY/AgRP (Neuropeptide Y/Agouti—related peptide) neurons

Leptin stimulates POMC/CART neurons to produce anorexigenic neuropeptide: melanocytes stimulating hormone that results in

1.Endocrine changes

2.Increase sympathetic nerve activity

This stimulates energy expenditure.

Leptin inhibits NPY/AgRP neurons that produce feeding—inducing (orexigenic) neuropeptide: NPY that results in inhibition of food intake.

The binding of leptin to its receptor initiates numerous signal transduction pathways and as result, regulates a range of cellular function in body (**Figure 1**). leptin receptor as a member of type 1 cytokine receptor family, signals via Janus kinase family of tyrosine kinase. Leptin induced dimerization alters the intracellular domain confirmation to increase its affinity for cystolic JAK. After this JAK activate and phosphorylate tyrosine residue, then it bind another free moving protein STAT. This also phosphorylate by JAK. Pairs of phosphorylated STAT dimerize and translocate to the nucleus to regulate gene transcription resulting in a biological response of leptin [7, 8].
