Metabolic homeostasis involves balancing catabolic and anabolic processes to maintain internal stability and allow growth. The AMP-dependent protein kinase (AMPK) regulates metabolic homeostasis by activating catabolism to produce ATP during low energy states and inhibiting anabolism to conserve ATP. Hormones like adiponectin, leptin, and ghrelin also control metabolic homeostasis by regulating AMPK activity and appetite. Disruptions to metabolic homeostasis can lead to diseases like diabetes mellitus.

1. METABOLIC
HOMEOSTASIS.
Sayali.R.Zende
MSc.-I
Roll.No:-24

2. What is Metabolism , Homeostasis & Metabolic Homeostasis?
 It is a biological process.
 Catabolism Anabolism.
 lead to growth & reproduction
& allow to maintain their
structures and respond to the
surrounding environment.
 Regulates the internal
environment
 It is a state of steady, to
maintained the condition.
 Optimal for the organisms.

3. AMP-dependent protein kinase(AMPK).
Regulate Metabolic Homeostasis.
Activates Catabolism ATP.
Inhibits Anabolism to conserved ATP.
It targets include the heart isozyme of the bifunctional enzyme PFK-2/FBPase-2 which control
(F2,6P) concentration.
Ischemic Diseases (deficient supply of blood to a body part)
Oxygen Oxidative Phosphorylation [Concentration of ATP.]
AMP buildup Anaerobic Glycolysis [ ATP production.]
SWITCH

4. AMPK
Promotes Inhibits
• Fatty acid Oxidation
• Glucose Uptake.
• Lipogenesis
• Cholesterol Synthesis
• Gluconeogenesis in
Liver
• Glycogen Synthesis in
Skeletal Muscle.
• Fatty acid Synthesis &
Lipolysis in Adipocytes.

5. Adiponectin
It regulates AMPK activity.
247- residue protein hormone, secreted by adipocytes.
[ Energy homeostasis, Glucose & Lipid metabolism by controlling AMPK activity]
The binding of adiponectin to it’s receptors i.e. on the surface of liver & muscle cells. Increases
phosphorylation & activity of AMPK.
It Inhibits: Gluconeogenesis
Stimulates: Fatty acid oxidation in liver, Glucose uptake. Also in Muscles.
Increases Insulin sensitivity.
Hormone decreases lead to various diseases. (Type 2 Diabetes)

6. Leptin
 Leptin expressed by adipocytes, provide
information to brain , how much body carries
the fat.
 Control energy expenditure.
 Leptin concentration increases with the
percentage of body fat.
 Develop leptin resistance

7. Ghrelin
 It is 28- residue peptide.
 It is an appetite stimulating gastric peptide,
that is secreted by the empty stomach.
 Decrease in ghrelin (obesity & high caloric
intake)
 Increases in ghrelin because of fasting.

8. Control of energy expenditure by Adaptive
Thermogenesis.
 The energy is utilized by an
organisms either by
performance of work or the
generation of heat.
 The other diet-induced
thermogenesis & form of
adaptive thermogenesis.
Norepinephrine
Release
Binds
Adernergic receptor
on brown fat
Increases cAMP,
enzymatic phosphorylation
Activates
Hormone sensitive Triacylglycerol
lipase
Increases free fatty acid
fuel
Oxidation.
Opening of protein
channel [UCP1] or
Thermogenin
ATP production
Heat
Mechanism of Thermogenesis

9. Hormones that control the appetite.
Leptin & Insulin is circulated in the
blood at proportional to body fat.
 appetite by inhibiting NPY/AgRP
neurons, which increases appetite
also activation of this neuron
inhibits melanocortin production.
Ghrelin is stimulated by activation
of NPY/AgRP. PYY3-36 Inhibits.
Stimulate Melanocortins neurons
in hypothalamus. It decreases the
appetite.

10. Metabolic Adaptation: Diabetes Mellitus.
 Insulin either is not secreted in sufficient amount or does not
efficiently stimulate its target cells.
 As a result blood glucose level increases.
Type I : (IDDM) or Juveneile-onset diabetes mellitus.
( childhood)
Type II : (NIDDM) or Maturity-onset diabetes mellitus.
( after 40)
Type I : β- cell transplant.
Metformin &
Thiazolidinediones (TZDs)
Proper diet.

11. Metabolic Adaptation: Insulin Signaling & Diabetes
Mellitus
Insulin signaling: The mechanism through which high concentration of free fatty acids
causes insulin resistance
Fatty acyl-CoA.
Diacylglycerols
Ceramides.
PKC
Insulin receptor substrate 1 (IRS-1)
Phosphoinositide 3-kinases (Pi3K)
Glucose transporter type 4 (GLUT4)

12. Starve-Feed Cycle.
 Food Intake & starvation Induce Metabolic Changes.
 Insulin signals the fed state: glycogen &
triacylglycerols & the synthesis of proteins.
 Glucagon signals a low blood glucose level: glycogen
breakdown & gluconeogenesis & triacylglycerol
hydrolysis .
 After a meal, the rise in blood glucose level lead to
increases the secretion of insulin and decrease
secretion of glucagon.
 The liver and muscle then use fatty acids instead of
glucose to meet their own energy needs so that
glucose is conserved for use by the brain.
 Protein degradation minimized , large amount of
ketone bodies are used then its use as major fuel.
Well- Fed State: Insulinemia (food take
the diet supplies the energy
requirements.)
In Early Fasting State & In Fasting State
: Insulinemia , Glucagonemia.

13. Target of Rapamycin (TOR)
 Discovered in 1991.
 It a Lipophilic macrolide, secondary metabolite produce
by Streptomyces Hygroscopicus.
 Isolated from an soil sample in Rapa-Niu (Easter Island
in1965).
 Initially used as antifungal agent.
 Immunosuppressant for treatment of allograft
rejection. Also inhibit the proliferation of tumor cells.
 It’s clinical application in three major therapeutic areas:
Organ transplantation, Cancer & coronary artery
diseases.
 It’s a key component that co-ordinately regulates the
balance between growth & autophagy in response to
cellular physiological condition & environmental stress.

14. .