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Regulation of Body Weight Regulation of body weight and set ... - PowerPoint PPT Presentation


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Regulation of Body Weight Regulation of body weight and set point theory. Leptin and body weight regulation. Melanocortin system: anorexigenic signaling. NPY and AGRP: orexigenic signaling. Putting it all together. Theories of Obesity

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slide1

Regulation of Body Weight

Regulation of body weight and set point theory.

Leptin and body weight regulation.

Melanocortin system: anorexigenic signaling.

NPY and AGRP: orexigenic signaling.

Putting it all together.

slide2

Theories of Obesity

  • Can BW be regulated in the face of high or low caloric consumption (Jules Hirsch, early 1970’s)???
  • Subjects
  • 100 healthy male volunteers with stable body weight for at least 6 months
  • three groups: thin, healthy weight, and overweight
  • confined to a sedentary life in a metabolic ward of a hospital
  • Design
  • food availability was systematically varied to promote:
    • a 10% BW gain
    • a 10% BW loss
  • measurements:
    • body weight, body mass index
    • food intake
    • feelings of hunger/satiety
    • mood
slide3

165 lbs

+ 10%

150 lbs

- 10%

135 lbs

“Fattening Phase”

  • forced to increase intake
  • hi fat diet
  • hi carbohydrate diet

“Slimming Phase”

  • caloric restriction
  • low fat diet
  • low carbohydrate diet
slide4

165 lbs

+ 10%

150 lbs

- 10%

135 lbs

  • Results – Following a 10% body weight loss
    • increase in appetite
    • food obsessions
    • felt sluggish
    • decrease in metabolic rate
  • When given free access to food, subjects
    • consumed larger meals
    • consumed more frequent meals
    • re-gained the weight lost during the “slimming phase”
slide5

165 lbs

+ 10%

150 lbs

- 10%

135 lbs

  • Results – Following a 10% body weight gain
    • decrease in appetite
    • food aversions
    • bloating, gastrointestinal distress
    • increase in metabolic rate
  • When given free access to food, subjects
    • consumed smaller meals
    • consumed less frequent meals
    • chose foods that were low in fat content
    • lost the weight gained during the “fattening” phase
slide6

165 lbs

+ 10%

150 lbs

- 10%

135 lbs

  • Conclusions
    • body weight is a regulated variable
    • transient behavioral changes
    • (i.e., over/under-eating) induces
    • behavioral (appetite) and physiological
    • (metabolic) changes that help to “defend”
    • a person’s body weight

increased

satiety

signaling

  • The Big Question….
  • Well, there are actually 2….
    • How does the brain sense the body’s
    • level of adiposity stores?
    • If our body weights are regulated, how does
    • one become overweight/obese or maintain
    • a significant weight loss?

increased

orexigenic

signaling

slide7

leptin

leptin

brain

Factors that Regulate Body Weight

  • Leptin
  • protein product of the ob gene (also called OB protein)
  • synthesized in white adipose tissue
  • secreted in proportion to body adiposity
  • functions as a hormone
  • binds to leptin receptor (OB-R) in the brain
  • acts on multiple brain regions (ARC, VMH, DMH)
  • expression is sexually dimorphic
slide8

Melanocortin System

  • family of peptides cleaved from the proopiomelanoocortin (POMC) precursor
  • POMC neurons are expressed solely in the arcuate nucleus (ARC)
  • one product of POMC neurons is aMSH

aMSH

POMC protein

  • aMSH
  • alpha-melanocyte-stimulating hormone
  • synthesized within POMC neurons; secreted from the PVN
  • binds with melanocortin receptors in the PVN (MC4 receptor)
  • decreases food intake
  • release of aMSH is regulated by leptin
  • POMC neurons contain leptin receptors (OB-R)
  • melanocortin receptor knockout mice
slide9

NPY

  • neuropeptide Y
  • neurotransmitter; widespread expression in the brain
  • multiple biological actions
      • suppress reproductive function
      • causes smooth muscle to relax
      • decreases grooming behavior (in rats!)
      • anxiolytic effects
      • increases food intake
  • synthesized in the arcuate nucleus (ARC)
  • secreted from the paraventricular nucleus (PVN) in
  • response to a decline in energy stores
  • central administration of NPY
      • increases food intake
      • increases fat storage
      • decreases metabolic energy expenditure
      • increases body weight
slide10

AGRP

  • agouti-related protein
  • synthesized in the ARC (co-localized with NPY)
  • secreted in the PVN
  • endogenous antagonist of MC-4 receptor
  • stimulates food intake and weight gain
  • also regulated by leptin
slide11

Activation of the Melanocortin System Inhibits Food Intake

Satiety Signal

Decrease

in Food Intake

PVN

MC4-R

ARC

slide12

+

+

Melanocortin System Is Modulated by Leptin

Increased Satiety Signal

Decrease

in Food Intake

PVN

MC4-R

OB-R

Increased

Leptin Secretion

ARC

slide13

Melanocortin System Is Modulated by Leptin

Decreased Satiety Signal

Increase

in Food Intake

PVN

-

MC4-R

OB-R

+

Decreased

Leptin Secretion

ARC

slide14

Orexigenic Signal

Increase

in Food Intake

  • AGRP
  • agouti-related protein
  • synthesized in the ARC (co-localized with NPY)
  • secreted in the PVN
  • endogenous antagonist of MC-4 receptor
  • stimulates food intake and weight gain
  • also regulated by leptin

PVN

ARC

slide15

Satiety Signal

Decrease

in Food Intake

PVN

+

-

ARC

Dual Systems Function to Keep Body Weight Stable

slide16

How Does Leptin Regulate Body Adiposity?

% body fat

A)Healthy BW:Leptin secretion is stable and supports energy balance (FI = EE).

B)Healthy BW:Decrease in leptin secretion signals a decrease in adipose stores and produces a positive energy balance (FI > EE).

C)Healthy BW:Increase in leptin secretion signals an increase in adipose stores and produces a negative energy balance (FI < EE).

D)Obese:Set point is elevated. Increase in leptin secretion fails to signal an increase in adipose stores and, thereby, fails to produce a negative energy balance (FI = EE). ** WHY ???

slide17

OVEREAT

brain senses

rise in plasma leptin

1) appetite is suppressed

2) metabolism increases

Increased

Leptin Secretion

In an Individual with a Healthy Body Weight….

slide18

In an Overweight Individual….

OVEREAT

brain senses

rise in plasma leptin

1) appetite is not suppressed

2) metabolism doesn’t change

Increased

Leptin Secretion

slide19

In an Individual with a Healthy Body Weight….

Increased release of a-MSH

Decreased release of AGRP

Decreased release of NPY

OVEREAT

brain senses

excessive calories

1) appetite is suppressed

2) metabolism increases

Increased

Leptin Secretion

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