Link between obesity and sleep loss

Energy conservation may be a major function of sleep, according to new study in worms

April 22, 2020

Science Daily/University of Pennsylvania School of Medicine

Can staying up late make you fat? A growing body of research has suggested that poor sleep quality is linked to an increased risk of obesity by deregulating appetite, which in turn leads to more calorie consumption.

But a new study published this week in PLOS Biology found that the direction of this reaction might actually be flipped: It's not the sleep loss that leads to obesity, but rather that excess weight can cause poor sleep, according to researchers from the University of Pennsylvania's Perelman School of Medicine and the University of Nevada, Reno, who discovered their findings in the microscopic worm Caenorhabditis elegans (C. elegans).

"We think that sleep is a function of the body trying to conserve energy in a setting where energetic levels are going down. Our findings suggest that if you were to fast for a day, we would predict you might get sleepy because your energetic stores would be depleted," said study co-author David Raizen, MD, PhD, an associate professor of Neurology and member of the Chronobiology and Sleep Institute at Penn.

Raizen emphasized that while these findings in worms may not translate directly to humans, C. elegans offer a surprisingly good model for studying mammalian slumber. Like all other animals that have nervous systems, they need sleep. But unlike humans, who have complex neural circuitry and are difficult to study, a C. elegans has only 302 neurons -- one of which scientists know for certain is a sleep regulator.

In humans, acute sleep disruption can result in increased appetite and insulin resistance, and people who chronically get fewer than six hours of sleep per night are more likely be obese and diabetic. Moreover, starvation in humans, rats, fruit flies, and worms has been shown to affect sleep, indicating that it is regulated, at least in part, by nutrient availability. However, the ways in which sleeping and eating work in tandem has remained unclear.

"We wanted to know, what is sleep actually doing? Short sleep and other chronic conditions, like diabetes, are linked, but it's just an association. It's not clear if short sleep is causing the propensity for obesity, or that the obesity, perhaps, causes the propensity for short sleep," said study co-author Alexander van der Linden, PhD, an associate professor of Biology at the University of Nevada, Reno.

To study the association between metabolism and sleep, the researchers genetically modified C. elegans to "turn off" a neuron that controls sleep. These worms could still eat, breathe, and reproduce, but they lost their ability to sleep. With this neuron turned off, the researchers saw a severe drop in adenosine triphosphate (ATP) levels, which is the body's energy currency.

"That suggests that sleep is an attempt to conserve energy; it's not actually causing the loss of energy," Raizen explained.

In previous research, the van der Linden lab studied a gene in C. elegans called KIN-29. This gene is homologous to the Salt-Inducible Kinase (SIK-3) gene in humans, which was already known to signal sleep pressure. Surprisingly, when the researchers knocked out the KIN-29 gene to create sleepless worms, the mutant C. elegans accumulated excess fat -- resembling the human obesity condition -- even though their ATP levels lowered.

The researchers hypothesized that the release of fat stores is a mechanism for which sleep is promoted, and that the reason KIN-29 mutants did not sleep is because they were unable to liberate their fat. To test this hypothesis, the researchers again manipulated the KIN-29 mutant worms, this time expressing an enzyme that "freed" their fat. With that manipulation, the worms were again able to sleep.

Raizen said this could explain one reason why people with obesity may experience sleep problems. "There could be a signaling problem between the fat stores and the brain cells that control sleep," he said.

While there is still much to unravel about sleep, Raizen said that this paper takes the research community one step closer to understanding one of its core functions -- and how to treat common sleep disorders.

"There is a common, over-arching sentiment in the sleep field that sleep is all about the brain, or the nerve cells, and our work suggests that this isn't necessarily true," he said. "There is some complex interaction between the brain and the rest of the body that connects to sleep regulation."

https://www.sciencedaily.com/releases/2020/04/200422091205.htm

Inadequate sleep could cost countries billions

June 4, 2018

Science Daily/Oxford University Press USA

Inadequate sleep is a public health problem affecting more than one in three adults worldwide. A new study suggests that insufficient sleep could also have grave economic consequences.

Community sleep surveys suggest that inadequate sleep is substantial and increasing. Surveys performed several years ago demonstrated that complaints of inadequate sleep were common, with between 20 and 30 percent of respondents complaining of inadequate sleep on a regular basis across several Western nations. Recent surveys suggest this proportion is increasing; between 33 and 45 percent of Australian adults now have this complaint.

The growth of the problem over time is shared by other nations with similar demographics. Some 35 percent of U.S. adults are not getting the recommended 7 hours of sleep each night. About 30 percent of Canadians don't feel they're getting enough sleep. Some 37 percent of those in the UK, 28 percent of people in Singapore, and 26 percent of French people also report insufficient sleep.

Insufficient sleep is associated with lapses in attention and the inability to stay focused; reduced motivation; compromised problem solving; confusion, irritability and memory lapses; impaired communication; slowed or faulty information processing and judgment; diminished reaction times; and indifference and loss of empathy. Furthermore, short sleep increases the risk of heart attacks, stroke, hypertension, obesity, diabetes, and depression.

Here researchers attempted to measure the economic consequences of limited sleep times -- defined as "difficulties with sleep initiation, maintenance or quality associated with the presence of impaired daytime alertness" at least several days a week -- in Australia. Researchers evaluated financial and non-financial cost data derived from national surveys and databases. Costs considered included: financial costs associated with health care, informal care provided outside the healthcare sector, productivity losses, non-medical work and vehicle accident costs, deadweight loss through inefficiencies relating to lost taxation revenue and welfare payments; and nonfinancial costs of a loss of well-being.

The financial cost component was $17.88 billion, comprised of: direct health costs of $160 million for sleep disorders and $1.08 billion for associated conditions; productivity losses of $12.19 billion ($5.22 billion reduced employment, $0.61 billion premature death, $1.73 billion absenteeism, $4.63 billion lost through workers showing up for work but not actually performing work on the job); non-medical accident costs of $2.48 billion; informal care costs of $0.41 billion; and deadweight loss of $1.56 billion. The non-financial cost of reduced well-being was $27.33 billion. Thus, the estimated overall cost of inadequate sleep in Australia in 2016-17 (population: 24.8 million) was $45.21 billion.

The financial and non-financial costs associated with inadequate sleep are substantial. The estimated total financial cost of $17.88 billion represents 1.55% of Australian gross domestic product. The estimated non-financial cost of $27.33 billion represents 4.6% of the total Australian burden of disease for the year. The researchers argue that these costs warrant substantial investment in preventive health measures to address the issue through education and regulation.

In setting national health priorities, governments have attempted to identify issues that involve high communal illness and injury burden with associated high costs for attention through public education, regulation, and other initiatives to effect improvements in health status. The authors say that governments have been remarkably successful in targeting diabetes, depression, and smoking, for example. These data presented above suggest that sleep health may merit similar attention. The situation is likely to be similar in equivalent economies.

Researcher quote: "We are in the midst of a worldwide epidemic of inadequate sleep, some from clinical sleep disorders, some through pressure from competing work, social and family activities and some from failure to give sleep sufficient priority through choice or ignorance. Apart from its impact on well-being, this problem comes at a huge economic cost through its destructive effects on health, safety and productivity. Addressing the issue by education, regulation and other initiatives is likely to deliver substantial economic as well as health benefits."

https://www.sciencedaily.com/releases/2018/06/180604093111.htm