The Topeka Tubby Theory of Obesity

1-Chronic Obesity is due to dysfunction of Leptin and Insulin

Insulin peripherally is anabolic. It promotes constructive metabolism. Insulin will store fat in adipose and glycogen in muscle and liver.

Insulin centrally is catabolic. (like Leptin) Insulin breaks down molecules to release energy.. 

Low Leptin increases food intake and suppresses energy expenditure. (Youdim p6).

"Leptin is an important signal for starvation." 

High Leptin reduces food intake by inhibiting NPY/AgRP neurons and stimulating the alpha-MSH neurons. (Except in the OBESE who become Leptin “resistant". Only LEAN individuals appear to be regulating body weight.) 

Centrally, Leptin and Insulin share same feeding inhibitory and thermogenic pathways.

Here is rest of theory link

10 reasons why people remain thin

Part two of this discussion is found on 2009 BBC video link

10 Reasons Why People stay thin  

1- CCK

2- GLP-1

3- Oxyntomodulin

4- PYY

5- Amylin

6- Adiponectin

7- Pancreatic polypeptide PP

8- Serotonin

9- Insulin

10- Leptin


These are distal signals to the brain that regulate food intake and negative energy balance.  They reduce food intake and increase energy expenditure.

This system works very well in people who remain thin throughout their life.  I suspect these folks lack the 100+ genes that predispose folks to obesity.  FTO gene influences enhancers and repressors

People who have FTO genes and family history of insulin resistance easily overcome the 10 signals above because of abundance of food and dysregulation of dopamine homeostasis and hypodopaminergic reward deficiency syndrome. (Wang et al)

A major mistake in nutrition was to steer people away from fat intake in favor of more carbohydrate intake.  Pasta was even said to be a health food.

Another error that continues are guidelines telling folks to have a minimum of 175 grams of carbohydrates.

There are essential amino acids and fats that the body cannot make and must get from nutrition.

There are backups in the body to maintain glucose levels in absence of carbohydrate intake.

Gluconeogenesis makes glucose in the liver and kidneys from lactate and amino acids and keeps the fasting morning glucose at a normal level.

Free Fatty acids may be used as energy in heart and liver.

Ketones may be used as energy in the brain.

I raised my kids on skim milk have been taught fat was bad for arteries.

Now I believe that an egg is the perfect food as it contains all the essential amino acids that we need.

Nutritionists need to push protein for satiety and fat for taste.  Avoid carbohydrates to avoid insulin resistance developing.

Fruit is not a magical anti-oxidant treatment for long life.  It is God’s sugar.

Low glycemic carbohydrates with fiber are pushed as health foods.

If you are chronically constipated you may find high fiber food to be healthy.

If you have hypertension you may find yourself to be salt sensitive.

If you are prone to obesity you definitely want to avoid carbohydrates.

Despite the 10 signals listed above to keep you thin, abundant carbohydrates in genetically predisposed obese will lead to insulin resistance and central obesity with leptin resistance or elevated leptin threshold.

For the naturally thin, when offered a whole pizza pie they will happily eat only one slice.  The 10 signals work for them.

A new theory of Obesity

Obese individuals are Leptin resistant and often insulin resistant. 
Thus Leptin and Insulin acts differently in the obese state. 
They also act differently in the reduced obese state which is why people cannot maintain their weight loss despite low calorie diet and exercise. 

Get the details at the Sponge Theory of Obesity

link above