Hormone responses to signals of hunger and satiety

Are cases of obesity increasing globally?

Yes

What are some of the negative results of obesity?

• Type 2 diabetes

• Heart disease

• Stroke

• Some types of cancer

• Sleep apnea

• Hypercholesterolemia

What happens in the body during a well-fed state versus a fasting state?

• Well-fed:

  • Brain: Food → glucose, free fatty acids, amino acids. Glucose powers the brain and muscles

  • Liver: Glucose → glycogen. Stored in liver and muscles

  • Pancreas: Insulin facilitates glucose transportation

• Fasting state:

  • Brain: Free glucose and ketone bodies power the brain

  • Liver: Glycogenesis breaks down stored glycogen. Lipolysis releases free fatty acids and glycerol.

  • Pancreas: Glucagon is released

What signaling molecules are involved in the regulation of energy balance?

• Orexigenic signaling molecules- increase appetite

• Anorexigenic signaling molecules- decrease appetite

What are the internal signals that influence feeding behavior?

Available energy: glucose, fatty acids, ketone bodies

How does the body use glucose?

• Glucose can be oxidized into energy: glucose + oxygen = CO2 + H2O + ATP

• All body cells can use glucose for fuel (glycogenesis= Breaking down glycogen)

How does the body use fatty acids?

• All cells in the body can use fatty acids (via lipolysis)

• Mostly the heart uses fatty acids

What is the role of insulin in the body?

Insulin brings glucose into cells (except in the brain)

What happens with the absence of insulin?

• Hyperglycemia- high blood sugar

• Diabetes mellitus

  • Type 1- Can’t make insulin

  • Type 2- Body becomes insensitive to insulin

• Diabetes insipidus- Problems with ADH

  • Results in the inability to keep water in, and frequent urination

How does the body store fuel?

• Glycogen- Glucose → glycogen, and stored in the liver and muscle (insulin needed for storage)

• Fatty acids- Food → fatty acids (fuel)

• Triglycerides- Fatty acids + glycerol = triglycerides (don’t need insulin for storage)

How does insulin influence hunger?

• Insulin is secreted before you eat (controlled by internal clock + cephalic cues [food smell]), and increases hunger

• Insulin promotes glucose storage + prevents triglyceride breakdown

What are glycogen and triglycerides used for?

They are broken down into glucose and fatty acids

What area of the body needs a constant source of glucose?

The brain

How do we get energy out of (break down) the storage?

• Epinephrine- Released from the adrenal medulla. Breaks down glycogen and triglycerides.

• Glucagon- Released from pancreatic alpha cells. Breaks down glycogen

• Glucocorticoids- (corticosterone/cortisol) released from the adrenal cortex. Leads to breakdown of glycogen

What is the glucostatic hypothesis? What is the main problem with it?

• Brain monitors glucose levels.

• When glucose levels fall below a critical level, we get hungry

• Eating restores glucose levels and hunger

• Problem: People with diabetes have high levels of glucose, but are often hungry

What is the Lipostatic hypothesis? What is the main problem with it?

• Brain monitors fat stores

• When fat stores fall below a critical level, we get hungry

• Eating restores body fat and hunger

• Problem: Humans get hungry after just 4 hours, but don’t lose weight

What was the experiment to test glucose vs fatty acids?

• Energy availability is limited from either glucose or fatty acids

• 2-Deoxy-D-glucose (2DG)- Inhibits glycolysis (turning glucose into energy)

  • Blocks glucose- increases food intake + hyperglycemia

• Methyl palmoxirate- Inhibits lipolysis (breaks down triglyceride into glycerol and fatty acids)

  • Blocks fatty acid metabolism- Increases food intake

Which is a stronger signal to eat food, glucose or fatty acids?

Both are strong signals

What area of the body can strongly detect energy levels?

The liver- Nutrients infused through a vein (hepatic portal vein) in the liver decreases food intake. 2DG applied here increases food intake.

What does a large dose of insulin do?

Reduces blood glucose levels, makes animals hungry

What do ketone bodies do in the brain?

Makes the brain “fed”, does not inhibit insulin-induced food intake

What does fructose do in the brain?

Makes the liver “fed”, inhibits insulin-induced food intake

What happens if there is a “fed” liver and a “starved” brain?

• Blocks insulin-induced feeding

• Due to the vagus nerve (where the liver monitors glucose levels to the CNS)

• Cutting the vagus nerve blocks the effects of fructose in the liver

What are two rodent models for genetic obesity?

• Obese (ob/ob) mouse

• Zucker rat

What does leptin do to ob/ob mice? Why?

• Makes them thin

• ob/ob mice lack the leptin gene

What are zucker rats?

• Rats that have a mutation of the leptin receptor

• Gene therapy to replace the missing receptor reverses the effects

What is ghrelin?

• A gut peptide made by stomach cells.

• It rises before meals and falls after

• Ghrelin injections increase hunger

Why is it unlikely that ghrelin directly affects hunger signaling?

There are many other peptides that can decrease food intake

What is the dual center theory? Is it correct?

• The lateral hypothalamus is the hunger center, the ventromedial hypothalamus is the satiety center

• This theory is wrong

Why is the dual center hypothesis incorrect?

• Lesions of lateral hypothalamus results in sick mice (due to cutting dopamine off)

• Lesions of the ventromedial hypothalamus results in obese mice (due to increased fat stores, and insulin disruption)

What are the most popular amine and peptide neurotransmitters?

• Neuropeptide Y- increases food intake, has its own receptors, made by arcuate neuron

• AGRP- increases food intake, binds to another receptor (melanocortin), made by arcuate neuron

• POMC (α-MSH)- inhibits food intake, binds to melanocortin receptors, a melanocortin, made by arcuate neuron

• CART

What do GI hormones do?

Serve as satiety signals that converge on the dorsal hindbrain

What are the two main areas of the neural circuit involved with food intake?

• Paraventricular nuclei of hypothalamus (PVH)

  • Arcuate neurons project here

• Arcuate nuclei of hypothalamus (Arc)

  • Ghrelin, leptin, and insulin act here

What are incretins?

• A group of metabolic peptide hormones that lower blood glucose

• Glucagon-like-peptide 1 (GLP-1) and Gastric inhibitory protein (GIP)

• Stimulate insulin release, inhibit glucagon release (ultimately lowering blood glucose)