- Weight gain due to stress,
disrupted circadian rhythms and treatment with Steroid (glucocorticoid) drugs may be
dependent on the timing of hormonal pulses.
- Controlling the timing of the
stress hormone pulses may help in reducing weight gain.
- Fat-cell maturation ramps up if the trough in exposure to Steroid (glucocorticoid) lasts less than 12 hours.
The timing of the dips and rises
in the stress hormone-cortisol may explain why people gain weight due to
chronic stress, disrupted circadian rhythms and treatment with Steroid (glucocorticoid)
drugs, according to a new study. The findings published in Cell
suggest new strategies to reduce weight gain by
controlling the timing of hormonal pulses.
People with rheumatoid arthritis
and asthma are
most often prescribed Steroid (glucocorticoid) drugs in order to function normally but
these drugs cause significant weight gain as a side effect.
‘Controlling the timing of the hormonal pulses may help in reducing weight of patients who take glucocorticoid drugs for treating rheumatoid arthritis and asthma.’
"It (the study) explains why treatments with Steroid (glucocorticoid) drugs,
which are often essential for people with rheumatoid arthritis and asthma to
even function, are so linked with obesity
and it suggests ways in which such
treatments can be given safely without the common side effects of weight gain and
bone loss," said Mary Teruel, PhD, assistant professor of chemical and
systems biology and senior author of the study.
The hormone cycle
A healthy person's level of Steroids (glucocorticoids) rises and falls in a
circadian 24-hour cycle. The level reaches its peak around 8 a.m., drops to its lowest around 3 a.m. and the next day to rises back again to reach its peak about five hours later.
The rise in the hormone levels is a wake-up signal that gets us moving and turns on our appetites.
However, the Steroid (glucocorticoid) levels in our bloodstream can also be increased by
Our fat tissues contain excess precursor fat cells that can convert to
fat cells given the right signals. Steroids (Glucocorticoids) trigger these precursor
cells to convert to fat cells. In a healthy condition, less than 1% of a
person's precursor fat cells convert into fat cells. The low rate of conversion
is essential for replacing damaged mature cells and for renewing and
maintaining healthy fat tissue.
The study aimed to find out why in normal conditions, rising Steroid (glucocorticoid) levels due to circadian
rhythms and healthy short-term stresses don't cause all our precursor cells to
convert into fat cells, but in conditions of chronic stress
jet-lag and sleep disruption the conversion rate of
fat cells is much higher.
To do this the research team decided to study the timing of the
Steroid (glucocorticoid) pulses and its effect on fat cells.
Precursor fat cells were grown in petri dishes and exposed to Steroids (glucocorticoids) in carefully timed pulses over
the course of four days. It was found that one pulse of Steroids (glucocorticoids)
lasting 48 hours led most of the cells to differentiate, while shorter pulses
with at least 12 hours between them resulted in minimal differentiation.
The team studied how the precursors sense the duration of the hormonal
pulses and filter out short pulses by using single-cell live imaging to track
PPAR-gamma protein levels. When PPAR-gamma levels increase to a certain
threshold level in a fat precursor cell, the precursor cell will convert in to
a fat cell.
of the normal circadian rhythm for
Steroids (glucocorticoids) led to a doubling of the fat mass in animals due to both
the creation of new fat cells and the growth of existing fat cells.
is no increase in fat, as long as Steroid (glucocorticoid) boost was delivered by
injection, only during the normal circadian peak times, even if they
increased peak Steroid (glucocorticoid) levels forty-fold.
The research has implications for controlling weight
gain in humans, Teruel said. "Yes, the timing of your stress does matter.
Since conversion of precursor cells into fat cells occurs through a bistable
switch, it means you can control the process with pulsing. Our results suggest
that even if you get significantly stressed or treat your rheumatoid arthritis
with Steroids (glucocorticoids), you won't gain weight, as long as stress or
Steroid (glucocorticoid) treatment happens only during the day. But if you experience
chronic, continuous stress or take Steroids (glucocorticoids) at night, the resulting loss
of normal circadian Steroid (glucocorticoid) oscillations will result in significant
weight gain," she said.