We know stress and poor sleep are linked to weight gain, largely because they send hormones for a loop.
But for the first time ever, scientists have confirmed that the timing of those hormonal dips and rises are crucial.
In healthy people, fat cells turn over at a rate of 10 percent per year: when they die, they are replaced by new healthy fat cells.
Now, a team at Stanford University School of Medicine has confirmed how this regular rate relies on the day-night hormone cycle, and it is when that cycle is out of sync or operates at night that unhealthy fat starts to build, particularly in the belly.
It was a mystery long-plaguing science to discover what ‘flips the switch’ that leads to weight gain, and lead author Dr Mary Teruel says the research has implications for controlling weight gain in humans.
‘Yes, the timing of your stress does matter,’ Dr Teruel, assistant professor of chemical and systems biology, said.
‘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 glucocorticoids, you won’t gain weight, as long as stress or glucocorticoid treatment happens only during the day.
‘But if you experience chronic, continuous stress or take glucocorticoids at night, the resulting loss of normal circadian glucocorticoid oscillations will result in significant weight gain.’
In a healthy person, cortisol levels peak at around 8am, which wakes us up (in theory), and drop to their lowest at 3am the next day, before rising back to its peak five hours later.
Ideally, this 8am peak will be triggered by exposure to sunlight, if not an alarm. When it does, the adrenal glands and brain will start pumping adrenalin.
By mid-morning, the cortisol levels start dropping, while the adrenalin (for energy) and serotonin (a mood stabilizer) keep pumping.
At midday, metabolism and core body temperature ramp up, getting us hungry and ready to eat.
After noon, cortisol levels start their steady decline. Metabolism slows down and tiredness sets in. Gradually the serotonin turns into melatonin, which induces sleepiness. Our blood sugar levels decrease, and at 3am, when we are in the middle of our sleep, cortisol levels hit a 24-hour low.
During this cycle, we can experience some stressors without having to worry about our bellies bulging. A morning coffee or an afternoon workout, for example, will increase cortisol levels in our bloodstream temporarily in a positive way, boosting energy.
Underlying all of this is the fact that we all have an excess of ‘precursor’ fat cells, which could convert into fat if given the signal.
In healthy people, fewer than one percent of their precursor fat cells are converting into fat cells – a low rate of conversion which is key so that damaged mature cells can be replaced and healthy fat tissue can be maintained.
In people suffering chronic stress, jet lag, or working night shifts, this conversion can go into overdrive, turning precursor cells into fat that start to balloon the person’s body.
While we knew cortisol was inextricably linked with fat conversion, we have never been able to explain exactly what kept this balance in check.
‘What stops normal, healthy daily increases in our glucocorticoid levels [which includes cortisol] due to circadian rhythms and healthy short-term stresses from causing all our precursor cells to convert into fat cells?’ Dr Teruel asked.
‘Why aren’t we drowning in fat every time glucocorticoid levels go high in the morning due to normal circadian rhythms or when our glucocorticoid levels spike when we exercise or go from a warm building out into the cold?
‘And why is losing the normal rhythm of glucocorticoid secretion – such as in conditions of chronic stress, jetlag and sleep disruption in shift-workers – so linked to obesity?’
To find an answer, Dr Teruel decided to become the first to investigate the timing of glucocorticoid ‘pulses’ (dips and rises).
Dr Teruel found that rises in levels of the ‘stress hormone’ (cortisol) are beneficial if it happens during the day, and lasts fewer than 12 hours: it gets to work breaking glucose down from stored fat to boost energy.
But chronic stress and night shifts can send cortisol levels spiking at night, or even soaring for more than 24 hours – and that is when cortisol’s fat-busting becomes a problem, saturating the body with glucose that turns into unhealthy body fat.
‘It explains why treatments with 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,’ Dr Teruel added.
To investigate this, Dr Teruel worked with graduate students Zahra Bahrami-Nejad and Michael Zhao to expose precursor fat cells to glucocorticoids in carefully timed pulses over the course of four days.
Every other day they bathed the petri-dish-grown cells in fluids with and without glucocorticoids, to assure that the total exposure to the hormone remained the same.
Scanning the cells, they found that one pulse of glucocorticoids lasting 48 hours led most of the cells to differentiate. Meanwhile, shorter pulses with at least 12 hours between them resulted in minimal differentiation.
The link between food and glucocorticoids is not well-understood, Teruel said. Some of her newer experiments aim to understand how food, insulin and glucocorticoids are related.
