Leptin, the Hunger Hormone

"The journey through obesity and chronic metabolic disease begins and ends with the hormone insulin, the energy storage hormone [...]. There is no fat accumulation without insulin. Insulin shunts sugar to fat. It makes your fat cells grow. The more insulin, the more fat, period." (my emphasis)

                                                  - Dr Robert H. Lustig, Fat Chance

Now, let's see the effect of leptin on our weight:

Leptin is a hormone released by the fat tissue into the bloodstream. When it reaches the brain, more specifically the hypothalamus, it signals to the brain that there's enough energy stored in the fat tissues, and tells us "you don't need another Mars bar". The level of circulating leptin is proportional to body fat. The more body fat, the more leptin in the bloodstream.

"When fat mass falls, plasma leptin levels fall stimulating appetite and suppressing energy expenditure until fat mass is restored. When fat mass increases, leptin levels increase, suppressing appetite until weight is lost. This physiological system ensures that total energy stores are stably maintained within a relatively narrow range."
                                                  - (Wikipedia)

And here are the steps:

1. When fat cells are empty,
2. There is no leptin production, the brain interprets it as "starvation",
3. So, we start to eat.
4. As we eat, our insulin goes up, this will help to put the energy into the fat tissues. And when the fat cells are full, 
5. Leptin production starts and signals the brain
6. To stop eating.

Under normal circumstances, this mechanism helps to keep a healthy weight and regulate the amount of food we eat. But, what happens when we gain weight? Normally as you eat, your growing fat tissues should produce more and more leptin to signal satiety to the brain. But, what happens when the brain is not able to see the leptin, when we are leptin resistant?

The brain is blind to leptin, and it interprets it as "starvation". In starvation mode:

• The brains sends a signal to our pancreas to secrete more insulin to prepare for bad times and to store whatever energy comes by.
• The brain also tells the body to reduce energy expenditure. This results in "lazy" behavior.
• Our brains also tells us to eat. This is the behavior interpreted as "gluttony" in our society.

When insulin goes up again, energy will be stored in the fat tissues, overloading the brain with leptin and insulin, the brain cannot see leptin, so it goes to starvation mode... and this goes on for years and decades.

Leptin is an important hunger regulating hormone. But, the prerequisite for a functioning leptin signaling system is low insulin levels. Insulin overload results in leptin resistance.

"[...] insulin can block leptin signaling in the brain, and therefore insulin acts as a 'leptin antagonist'. Many scientists have now shown that insulin actions in the [brain] block leptin signaling. A reduction in insulin concentration results in a decline in leptin. Insulin and leptin are independent hormones that bind to separate receptors in the [brain]. They have their own separate pathways of action, but they share the same signaling cascade. When insulin levels [in the brain] are chronically high, leptin cannot signal the hypothalamus." (my emphasis)
                                                           - Dr Robert H. Lustig, Fat Chance