Although science is still unraveling the complex influences of hormones, nerve
signals, and other factors that regulate appetite, food consumption, metabolism,
storage of energy in the form of fat and body weight, what follows is a simplified
description of what is known.

The hypothalamus of the brain receives minute-to-minute information about hunger
and satiety, but it also receives longer-term information about the body’s fat stores.
The hypothalamus monitors and regulates the body’s fat stores by responding to
levels of various hormones, including insulin and leptin—they are the main
messengers. In addition to leptin, another hormone, ghrelin, regulates appetite. Ghrelin is produced
by the stomach when empty, during fasting, or when dieting and often peaks
just before meal-times. Ghrelin stimulates appetite and promotes fat storage. A
satisfying meal, and also being overweight, decreases the production of ghrelin and
reduces appetite.

Other hormones are produced by the intestines after a meal. They
include cholecystokinin (CCK) and peptide YY (PYY). They have the opposite
effect of ghrelin; they suppress appetite. These gut hormones, with their opposing
effects, are considered to be the influences mainly responsible for the short-term,
hour-to-hour, and minute-to-minute regulation of appetite. Ghrelin influences the
hypothalamus and also has been shown to act on the reward centers of the brain.

Leptin is among about a dozen hormones that are synthesized by adipose tissue.
Leptin is produced in amounts proportional to the fat that adipose tissue contains,
so when the body’s level of fat increases, more leptin is synthesized. The hypothalamus
responds to leptin messages with one of two signals. High levels of leptin
lead the hypothalamus to turn off the vagus nerve, stimulate the sympathetic nervous
system to increase physical activity and metabolism to expend more energy,
suppress appetite, make us feel good, and lose fat. Low levels of leptin have the
opposite effect. They stimulate the parasympathetic system through the vagus nerve
that tells our digestive organs to store energy—including stimulating the pancreas
to release more of the insulin that promotes energy storage—and make us feel hungry
and unwell.

When leptin signaling is normal, you maintain energy balance at what Lustig calls
a “personal leptin threshold” that is also sometimes called a set point. The theory
is that the brain uses its regulatory mechanisms to maintain a genetically predetermined
weight and level of body fat—a set point. When this regulatory system
works well, leptin signals the body that you have enough energy on board, to expend
any excess energy, and to keep food intake low. But what if leptin signaling
doesn’t work or your set point is too high? If your hypothalamus does not respond
appropriately to leptin, your brain interprets this as too little fat on board—that you
need food. This inappropriately turns on the cycle of vagus nerve stimulation and
insulin release, more fat storage (to boost leptin), and obesity results. According to
Lustig, both obese and starving people have many of the same symptoms—fatigue,
malaise, and depression.

Normally leptin suppresses the release of dopamine and reduces the reward of food.
But if you are leptin resistant, dopamine is not cleared away, and you will want to
keep on eating because food will continue to be rewarding. Insulin also clears away
dopamine, so in a normal person, food would induce the release of insulin and attenuate the reward of more food. But if you are insulin resistant, this does not happen, and more food than you need for energy balance will continue to be pleasurable and
likely to be eaten. As Lustig has described it, “Starvation and reward conspire to thwart every obese person.”

The failure of the hypothalamus to respond appropriately to leptin is one key to
the obesity epidemic. The bodies of most overweight people are resistant to the
effects of leptin, and leptin has not been an effective drug to help control weight.
So then the question is, what causes leptin resistance? It turns out that when insulin
levels are chronically high, leptin cannot signal the hypothalamus because high insulin
acts as a leptin antagonist. So, then the next question is: Why are insulin levels
chronically high? The answer is mainly that the foods we consume are full of added
sugars and highly refined carbohydrates.

This blog presents opinions and ideas and is intended to provide helpful general information. I am not engaged in rendering advice or services to the individual reader. The ideas, procedures and suggestions in that are presented are not in any way a substitute for the advice and care of the reader’s own physician or other medical professional based on the reader’s own individual conditions, symptoms or concerns. If the reader needs personal medical, health, dietary, exercise or other assistance or advice the reader should consult a physician and/or other qualified health professionals. The author specifically disclaims all responsibility for any injury, damage or loss that the reader may incur as a direct or indirect consequence of following any directions or suggestions given in this blog or participating in any programs described in this blog or in the book, The Building Blocks of Health––How to Optimize Your Health with a Lifestyle Checklist (available in print or downloaded at Amazon, Apple, Barnes and Noble and elsewhere). Copyright 2021 by J. Joseph Speidel.