REGULATION

Adipose tissue hormones:

• Leptin, adiponectin (adipokines)
• Role as an endocrine organ

Leptin
• Stimulates energy use and limiting food intake

Adiponectin
• Modulates glucose and lipid metabolism in muscle and liver
• Enhances the sensitivity of tissues to insulin.
In adipose tissue glucose
a)oxidation to CO2 (TCA)
b)oxidation in PPP
,
c)conversion to long-chain fatty acids b

d)formation of acylglycerol through glycerol

3-phosphate a
c d
Gucose utilization  a larger proportion
oxidized to CO2 and converted to FA.

 glucose utilization  greater proportion

forms glycerol 3-phosphate for
esterification of acylCoA, minimize the
efflux of FFA.
• Adipose tissue TG lipolysis (hydrolysis) - reesterification

• Different pathways, reactants and enzymes

• Regulated separately  nutritional, metabolic, and hormonal

• The balance determines the magnitude of[FFA] pool adipose

tissue → determines [FFA] plasma
• Esp. plasma [FFA] on tissues, liver, muscle met.
Lipolysis cycle and reesterification

• TG → FFA + glycerol (HSL)

• Glycerol → blood → tissues (glycerol kinase (+)

,liver, kidney) → gluconeogenesis

• FFA (adipose tissue) → acyl-CoA (cyl-CoA

synthetase) → TG (reesterification with glycerol-3-
phosphate)

• Continuous cycle of lipolysis and reesterification

within the tissue

• If reesterification is not sufficient FFA

accumulation → plasma, binding to albumin and
plasma [FFA] 
 REGULATION OF FA RELEASE BY GLYCERONEOGENESIS

• FA released from adipose tissue or

used to resynthesize TG to limit FA
release into the circulation.

• TG resynthesis depends on supply of

glycerol 3-phosphate  dependent on
adipose glyceroneogenesis (synthesis of
new glycerol).
 REGULATION OF FA RELEASE BY GLYCERONEOGENESIS
In adipocyte,
• TG → glycerol + 3FFA (hormone-sensitive lipase)
• Glycerol to the liver for gluconeogenesis;
• Lactat → pyruvate → OAA (pyruvate carboxylase)
• Aa → OAA through TCA
• glycerol 3-phosphate synthesized from C of amino
acids, lactate, or pyruvate. PEPCK key enzyme
• Glucagon or epinephrine → cAMP  → PEPCK
stimulation (release of FA to the circulation)
• OAA → PEP → DHAP → glycerol 3-P →
reesterified to TG → exported from adipocyte

• 30% to 40% of the released fatty acids are

reesterified to triglyceride without leaving the
adipocyte.
Glucocorticoids: Thiazolidinediones
treat type 2 diabetes
• Liver stimulate activate a nuclear receptor called peroxisome
glyceroneogenesis and proliferator-activated receptor (PPAR),
gluconeogenesis induces the activity of PEP carboxykinase
• adipose tissue suppres increase the rate of glyceroneogenesis
glyceroneogenesis in the increasing the resynthesis of triacylglycerol in
by PEPCK expression adipose tissue and reducing the amount of
free fatty acid in the blood 8
 HORMONES
• Glucose and insulin increase uptake of glucose into adipose cells (GLUT 4)

Insulin 
• Inhibition: release of FFA from adipose tissue → plasma [FFA] 
• Increase: lipogenesis
ox. of glucose by PPP to CO2
pyruvate dehydrogenase, AcetylCoA Carboxylase activities

• Inhibit adipose tissue HSL activity → release of FFA, glycerol ,

• Adipose tissue is much more sensitive to insulin

• Epinephrine, norepinephrine, glucagon, adrenocorticotropic hormone
(ACTH), -melanocyte-stimulating hormone (MSH), thyroid-
stimulating hormone (TSH), growth hormone (GH), and vasopressin 
hormone-sensitive lipase activation
• Increase lypolysis
• plasma [FFA] 
• For optimal effect, most lipolytic processes require presence of
glucocorticoids and thyroid hormones.

• hormone-sensitive lipase inactivation: insulin, prostaglandin E1, and

nicotinic acid
Liver ketone β-oxidation
Adipose tissue:
TG high
insulin/glucagon ↑
LPL synthesized →
capillaries of adipose tissue
→
VLDL-Chylomicron
(endogenous and exogenous)
TG hydrolysed →
FA enter adipocyte →
FA +glycerol3-P (from
glucose)→ TG

Adipose tissue  glycerol

kinase
Glycerol → liver → TG

13
 acetyl-CoA carboxylase activation; AMP

inactivation  PKA cAMP-dependent

phosphorylation, ATP

ATP  → kinase inhibited, ACC

dephosphorylated (activated) →
stimulate malonyl-CoA adipose tissue
(FA synthesis) and
inhibition FA oxidation muscle cells

ATP  AMP  AMPK activated → ACC

phosphorylated (inactivate) → malonyl-
CoA  → FA synthesis  in adipose
tissue, FA oxidation  in muscle to
provide ATP

Insulin, activates ACC

Glucagon:insulin ratio determines the rate
citrate stimulates acetyl-CoA carboxylase and direction of FA metabolism.
• Allosterically activates
• Palmitoyl-CoA inhibits

• Low energy level →

phosphorylation (AMP-
activated PK) → inhibition
→ malonyl-CoA  → FA
synthesis  in adipose
tissue, FA oxidation  in
muscle to provide ATP
FA ox inhibition and FA
synthesis stimulation:

inhibition of carnitine
palmitoyl transferase I by
malonyl-CoA

Prevents newly
synthesized FA away from
mitochondria, β-oxidation
Short-term regulation
• Substrate availability, allosteric interactions, covalent
modification (phosphorylation)

Long-term regulation
• the amount of enzyme
• Changes in the rates of protein synthesis and/or breakdown.
• Synthesis of ACC and FAS, adipose tissue lipoprotein lipase 
stimulation by insulin and inhibition by starvation

• Glucose level effect insulin

Perilipin
• Perilipin, protein of lipid droplets in adipocytes
• Inhibits lipolysis by preventing access of the lipase enzymes
to the stored TG
• Hormones stimulating TG degradation  protein
phosphorylated → conformational change, expose the lipid
droplet surface to hormone-sensitive lipase, promote
lipolysis.