Chapter 14 The Major Motives of Life: Food, Love, Sex, and work 485initially thought that leptin might be the answer
to dieters’ prayers: Take leptin, lose weight! For
a minority of obese people who have a congeni-
tal leptin deficiency, that is true (Farooqi et al.,
2007). Alas, for most obese people, and for those
who are merely overweight, taking leptin does
not produce much weight loss (Comuzzie &
Allison, 1998).
Studies of mice suggest that leptin plays
its most crucial role during a critical period in
infancy, by altering the brain chemistry that
influences how much an animal or a person
later eats. More specifically, leptin helps regulate
body weight by strengthening neural circuits in
the hypothalamus that reduce appetite and by
weakening circuits that stimulate it (Elmquist
& Flier, 2004). Once those neural connections
are modified, the set point is, well, set (Bouret,
Draper, & Simerly, 2004). Some researchers
speculate that because of this early neural plas-
ticity, overfeeding infants while the hypothala-
mus is developing may later produce childhood
obesity.
Numerous other genes and body chemicals
are linked to appetite, metabolism, and being
overweight or obese (Farooqi & O’Rahilly, 2004;
Frayling et al., 2007; Herbert et al., 2006; Stice
et al., 2008). You have receptors in your nose and
mouth that keep urging you to eat more (“The
food is right there! It’s good! Eat!”), receptors in
your gut telling you to quit (“You’ve had enough
already!”), and leptin and other chemicals telling
you that you have stored enough fat or not enough.Genes also influence how much brown fat
a person has in addition to the usual white fat.
Brown fat is an energy-burning type of fat that
seems important in regulating body weight and
blood sugar. It is lacking in obese people, and may
be one reason that people who have excess fat
can’t burn all the calories they consume (Cypess
et al., 2009). However, production of brown fat is
also triggered by cold and exercise, which, in mice
at least, turns ordinary white fat brown (Ouellet
et al., 2012). Brown fat cells are vampires of the
metabolic system: When they run out of their
own sources of energy, they suck fat out of other
cells where it is stored throughout the body to
keep their proprietor warm. No, no, you can’t
(yet!) order a brown-fat supplement online.
When a mutation occurs in the genes that
regulate normal eating and weight control, the
result may be obesity. One gene, called obese, or
ob for short, causes fat cells to secrete a protein,
which researchers have named leptin (from the
Greek leptos, “slender”). Leptin travels through
the blood to the brain’s hypothalamus, which
is involved in the regulation of appetite. When
leptin levels are normal, people eat just enough
to maintain their weight. When a mutation of
the ob gene causes leptin levels to be too low,
however, the hypothalamus thinks the body lacks
fat reserves and signals the individual to overeat.
Injecting leptin into leptin-deficient mice reduces
the animals’ appetites, speeds up their metabo-
lisms, and makes them more active; as a result, the
animals shed weight. For this reason, researchers
Body weight and shape are strongly affected by genetic factors. Set-point
theory helps explain why the Pimas of the American Southwest gain weight
easily but lose it slowly, whereas the Bororo nomads of Nigeria can eat a lot of
food yet remain slender.