Leptin and Ghrelin: The Hunger Hormones

Chapter summary

Insulin, leptin, ghrelin and other hormones are linked. When they work together, the system is finely balanced.
When they fail, excess calories cause obesity and obesity worsens the excess.
Fructose interferes with all of them.
Eating is complicated. Over 40 hormones and many brain signals are involved, so “just drop the fork” ignores the biology.

Hypothalamus: The arcuate nucleus holds a hunger cell (NPY/AgRP), which makes you hungry and lowers metabolic rate, and a satiety cell (POMC), which makes you feel full and raises metabolic rate.
Ghrelin: made in the stomach. It switches on the hunger cell and off the satiety cell. It is also needed for good sleep.
Leptin: made in fat cells. It switches on the satiety cell and off the hunger cell.
Insulin: lowers ghrelin and raises leptin. Leptin in turn lowers insulin.
PYY: made in the ileum and colon. It rises after eating and works on NPY receptors.
Others include amylin, GLP-1, CCK, PP and oxyntomodulin.

Food shortage: Insulin falls, ghrelin rises and you feel hungry. Stored fatty acids are released.
Food surplus: The process runs in reverse and fat is stored. Hibernating mammals can double fat stores. The Western problem is continual gain, not seasonal gain.
Wait 15 to 20 minutes after eating for satiety hormones to act.
Fructose does not stimulate insulin, so it does not turn off ghrelin. Glucose and dairy sugars do.
Protein dampens hunger hormones.

Chronic excess raises insulin and pushes fat into fat cells, which release more leptin.
The body becomes resistant to leptin (like insulin resistance in diabetes) and ghrelin, and adiponectin falls.
Lower activity reduces the muscle enzyme that breaks down fat, which worsens insulin resistance.
High leptin and insulin switch off ghrelin cells, but the brain stops responding to leptin, so hunger persists.
A 2013 mouse study found another brain circuit (BNST) that drives gorging even when well fed.
Food matters: A Swedish study found an evening meal of brown beans, compared with white bread, cut glucose and insulin by 15%, raised PYY by 51% and lowered ghrelin by 14%.

Personal responsibility: Many say weight is control of the fork.
Biology view: Hormone disruption and genes (such as FTO) make hunger much harder to control for some people.
The author: Both matter. Hormones can be reset by changing what you eat, but the path back is not easy.

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