Leptin is a protein-hormone
that regulates appetite and
metabolism in humans and
other mammals. Leptin acts on
a very small region of the
brain called the hypothalamus
shown here:
Leptin was discovered by
researchers studing strains
of massively obese mice in
1994. It was found that
some strains of these mice
lacked the ability to
produce leptin while others
produced normal amounts
of leptin but lacked the
receptor protein needed in
the hypothalamus to
recognize leptin. When the
mice who had normal
receptors but couldn't
produce leptin were
injected with the protein,
they rapidly lost very large
amounts of weight. This
immediately suggested that
the protein could play a role
in treating human obesity
and several clinical trials
have been undertaken since
Unfortunately, leptin has not proved as effective in most people. In a very small
number of individuals who, like the mice described above, lack the ability to
produce leptin, the drug has dramatic effects, but in most people it is either
totally innefective or produces only slight weight loss. Still, the discovery of
leptin was a major breakthrough in the understanding of obesity.

Leptin Resistance

Leptin appears to fail in many people because they are resistant to it. In fact,
many obese people have much higher levels of leptin in blood than thin people.
This is true because generally, leptin is produced by fat cells and in proportion
to their number and size. Administering extra leptin to people who are resistant
to it doesn't help.

Fructose & Leptin Resistance

Research in 2008 showed that the sugar fructose (described at length here)
can, when consumed in large amounts by laboratory rats, cause the animals to
develop resistance to leptin in as little time as six months and worse,
silently--without causing the rats to gain weight--UNTIL the rats begin eating a
high fat diet at which point the former fructose eaters became significantly
more obese than their counterparts who were not fed fructose in the first
place. This suggests again that the sugar may be a prime culprit in weight gain
in humans.

Journal Reference:

1.Shapiro et al. Fructose-Induced Leptin Resistance Exacerbates
Weight Gain in Response to Subsequent High Fat Feeding. AJP
Regulatory Integrative and Comparative Physiology, October,
2008; DOI: 10.1152/ajpregu.00195.2008
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