Obesity, Leptin and Regulation of

Body mass
 Adipose tissue

-Adipose tissue is an anatomical term for loose connective tissue composed of

adipocytes (or fat cells).

-Its main role is to store

fatty acids in the form of
triglycerides, thus providing
the organism with effective
fuel storage

-Besides that it cushions and

thermally insulates the
body.

Adipose tissue Adipocyte + Capillary

 ADIPOSE TISSUE

Adipose tissue has an important endocrine function as it

produces adipokines and inflammatory mediators, amongst
others, leptin, adiponectin, resistin , adipsin, TNFα, IL-6 and
PAI-1

Because of the production of

inflammatory mediators, an
excess of adipose tissue leads to
a chronic mild inflammatory-
state that may play a role in
late onset diabetes (insulin
resistance).
subcutaneous
adipose tissue
 Role of Leptin
• Fat cells produce leptin and secrete it into the
bloodstream.

• Leptin works to suppress hunger

– Leptin receptors (ObR) are located in the hypothalamus

• Leptin’s effects on the arcuate neucleus are long-

lasting.

• Leptin activates POMC/CART neurons but inhibits

NPY/AgRP neurons
The Hypothalamus Coordinates Multiple
Systems That Control Hunger

• The arcuate nucleus of the hypothalamus contains an

appetite control circuits governed by hormones, such
as insulin.

• Other peripheral peptide hormones are

• Leptin
• Ghrelin
• PYY3–36
• CCK
 So Is leptin the cure for obesity?
• Percentage of people who are obese because they have a
mutation in the gene for Leptin = miniscule (only a few people
in the world have this mutation)

• Clinical trials a failure

– Daily leptin injections to obese patients
– Only a third of the patients lost weight
– patients dropped out of the study
– decreased appetite at first, and increased appetite after continued use
(leptin resistance)
– gained back the weight when the leptin injections ceased
 Why is Leptin Not The Miracle Cure for
Obesity?

➢In addition to leptin, there are many

hormones and neuropeptides that influence
appetite and obesity

➢ Giving leptin alone does not curtail obesity

➢Obese people have higher leptin than normal

weight people
 RED = INHIBITORY
GREEN = STIMULATORY

Leptin Insulin Ghrelin

NPY POMC (MSH)

Increases appetite Decreases appetite

 Increase Food Intake

• Orexin (lateral hypothalamus)

• NPY (arcuate and PVN)
• MCH (lateral hypothalamus)
 Dieting Doesn’t
Work

Dieting is a signal to the brain to

become better at storing fat
GHRELIN
 Role of Ghrelin
• Peptide hormone released from cells in the stomach
• Increases growth hormone secretion (GH-releasing)
• Increases during fasting and decreases after a meal
• Increased levels produce increased appetite
• Receptors located in the arcuate nucleus, lateral hypothalamic
area, accumbens nucleus, ventral tegmental area
• Obese individuals
– have low baseline levels
– levels do not drop after a meal so no signal for “just ate a
meal”
leptin

Refresh your memory: leptin in the arcuate

nucleus promotes POMC-neuron function
and inhibits Npy/AgRP-neurons, leading to an
anorectic signal (loss of apettite)
Integration of Appetite Signals in the
Hypothalamus