Analysis of Peptide YY 3-36 Structural Drug Design and Obesity

This report examines the structural drug design of Peptide YY 3-36 (PYY3-36), a hormone produced postprandially that regulates appetite. The report discusses the drug's mechanism of action, including its interaction with Y2 receptors, and its impact on feeding and satiety. It explores how PYY3-36 influences energy expenditure, potentially aiding in weight management. The report highlights the nutrient-dependent circulation of PYY and its site of action within the central nervous system, emphasizing the role of vagal afferents. It also analyzes the effects of PYY3-36 administration on feeding behavior and its potential in obesity treatment, including its ability to modulate the hedonic brain circuit. The report concludes by emphasizing the need for further research to fully understand the synthesis, action mechanisms, and release actions of PYY3-36.

PEPTIDE YY 3-36 STRUCTURAL DRUG DESIGN
INTRODUCTION
Peptides are chemical compounds whose functions depend upon shape and
sequence of amino acid chain. It also acts as hormone and can be used as
pharmacological compound which affects the satiety and feeding operations.
The structure based drug design can help to analyse its physiological and
pharmacology impact on feeding functionality.
Drug description
Peptide YY (PYY) is produced postprandially in ileum by endocrine cells in
response of meal energy. It regulates appetite. The compound can act with
neuropeptide and inhibits electrolyte secretions and gastro-intenstinal motility.
Thus, it gives indication of satiety by providing feedback signal in
hypothalamic circuit pathway. The hormone peptide YY 3-36 plays key role in
lowering the feeding and thus can be used for weight management or reduction.
It has been analysed that anorectic effect of the drug is caused by the Y2
receptors. The individuals with lower level of PYY reduces satiety and thus
affects the obesity development (Shi and et.al., 2017). The PYY is member of
peptide family and consist of pancreatic polypeptide and neruopeptide. They
share tertiary structure in which polyproline and alpha helix are joined by beta
turn.
Circulation
PYY circulation is nutrient dependent and is released from gut. The food
intake can increase its level while the fasting can lower its content. Due to this
reason after few hours of food intake PYY level is maximum. When intake
nutireint levels reach L cells, it initiates hormonal or neural actions. The
consistency of food, caloric load and composition of macronutrients also
influences the peak value of temporal profile of PYY.
Site of action
The Y2 receptors of PYY are located within vagal afferents, nodose ganglion
and throughout the central nervous system. Thus, principal action mechanism
is through vagal activation or its combination with the central action. It
enhances the probability of the PYY3-36 to influence the feeding impacts. The
drug follows hypothalamus path and other non-saturable mechanism. The
direct injections of PYY3-36 can help in lowering the feeding (Gonzalez and
Unniappan, 2016). The intra-arcuate injection of Y2 receptors can also be used
to block the anorectic impacts of peripheral drug administration. The vagas
role in mediating drug efect is controversial but the peripheral PYY3-36
enhances the vagal afferent firing. The infusion of PYY3-36 peptide with
functional MRI gives similar observations as provided by the neuronal
activities within hypothalamus and the mid brain regions. Thus, the drug
exerts its acts upon hedonic brain circuit and homeostatic for changing or
influencing feeding and satiety actions.
REFERENCES
Celik, A. and et.al., 2016. Effects of different metabolic states and surgical models on glucose metabolism and secretion of ileal L-cell peptides: protocol for a
cross-sectional study. BMJ open, 6(3), p.e010245.
Gonzalez, R. and Unniappan, S., 2016. Mass spectrometry-assisted confirmation of the inability of dipeptidyl peptidase-4 to cleave goldfish peptide YY (1–36)
and the lack of anorexigenic effects of peptide YY (3–36) in goldfish (Carassius auratus). Fish physiology and biochemistry, 42(3), pp.831-844.
Shi, Y.C., and et.al., 2017. Y5 receptor signalling counteracts the anorectic effects of PYY 3‐36 in diet‐induced obese mice. Journal of
neuroendocrinology, 29(10), p.e12483.
Impact of drug administration on feeding and satiety
The Y2 receptors mediate the PYY3-36 effects on feeding by showing high
resistance to anorectirc effects. The receptor can lower the adiposity and intake
of the food when it is administered peripherally. The dose dependent action of
PYY3-36 reduces food intake and appetite. Thus, it can be used as potential
theory of obesity control. The calorie intake in rodents is reduced in normal
living beings. However, the individuals who are deficient of DP-IV agrogate
inhibitory feeding effects. This is one of the reason that DP-IV inhibitors are
also used for the type 2 diabetes patients. A PYY3-36 injection into cerebral
ventricle, hippocampus and paraventricular nucleus stimulates the food intake
and delayed satiety in rodents.
The feeding effects generated by PYY depend upon the subtype of Y receptors
on which drug is activated. Along with the feeding the central drug
administration of PYY3-36 provides additional advantages of fuel partitioning
and energy expenditure. It alters the fat oxidation by encouraging its rate
through peripheral infusion (Celik and et.al., 2016).
There has been a negative correlation between energy rate of resting state and
fasting levels of PYY. The thermic effects of consumed food and postprandial
expenditure of energy is also associated with the PYY circulation level.
Hence, for regulation of the body weight PYY not only reduces food intake or
the feeding but it also enhances the energy expenditure.
CONCLUSION
It can be concluded that PYY3-36 can be used to regulate the energy balance
and feeding mechanisms. However, it is required that its synthesis, action
mechanism and release actions must be elucidated through advanced research.
It has been also analysed through drug design that PYY3-36 has potential to
modulate with the hedonic brain circuit and thus can be used to prepare
treatment methods of obesity which targets the PYY system.