Field Notes

Healthful Diet May Help Kidney Disease Patients Live Longer

A diet that emphasizes healthful foods rather than individual nutrients may help patients with chronic kidney disease live longer. The findings appear in the Clinical Journal of the American Society of Nephrology.

Patients with chronic kidney disease are advised to follow dietary recommendations that restrict individual nutrients such as phosphorus, potassium, protein, and sodium; however, empirical evidence suggests that these restrictions—which can be difficult to abide by—have limited effects on reducing patients’ risk of premature death.

Emerging evidence indicates that overall eating patterns may have greater effects on patients’ health and longevity. To investigate, a team led by Giovanni Strippoli, MD, PhD, of the University of Bari in Italy and Diaverum in Sweden; and Jaimon Kelly of Bond University in Australia, analyzed the medical literature, finding seven relevant studies that included a total of 15,285 participants.

Healthful dietary patterns generally were higher in fruits, vegetables, fish, legumes, cereals, whole grains, and fiber, and they were lower in red meat, salt, and refined sugars. In six studies, healthful dietary patterns consistently were associated with a 20% to 30% lower rate of mortality, with 46 fewer deaths per 1,000 people over five years. There was no significant association between healthful dietary patterns and risk of kidney failure.

“Chronic kidney disease now affects about 10% to 13% of the adult population and substantially increases risks of cardiovascular complications and early death,” Strippoli says. “In the absence of randomized trials and large individual cohort studies, this study is the best available evidence to drive clinical decision-making by patients and doctors on whole dietary approaches in chronic kidney disease.”

— Source: American Society of Nephrology


Neural Circuit That Helps Regulate Eating Identified

Beth Israel Deaconess Medical Center (BIDMC) researchers have identified previously unknown neural circuitry that plays a role in promoting satiety. The discovery revises the current models for homeostatic control—the mechanisms by which the brain maintains the body’s status quo—of feeding behavior. Published online in Nature Neuroscience, the findings offer new insight into the regulation of hunger and satiety and could help researchers find solutions to the ongoing obesity epidemic.

“Current models lack a rapidly acting satiety mechanism analogous to the hunger-promoting neurons,” says corresponding author Bradford B. Lowell, MD, PhD, a professor of medicine in the division of endocrinology, diabetes, and metabolism at BIDMC. “This component we identified provides the full ‘yang’ to the hunger-promoting neurons’ ‘yin.’”

Researchers have long known that hunger is regulated by two kinds of neurons: agouti-related protein (AgRP) neurons and pro-opiomelanocortin (POMC) neurons. AgRP neurons drive hunger; stimulating these nerves triggers eating within minutes. The opposing group of neurons, POMC, has been shown to promote satiety. Lab mice engineered to lack POMC neurons eat large quantities of food and become massively obese.

However, in recent years, new technology has allowed scientists to selectively manipulate neurons in living animals, demonstrating specific neurons’ direct effect on behavior. About five years ago, this type of research revealed that POMC neurons act over the course of many hours—not minutes like their AgRP counterparts.

“The lack of a rapid effect strongly suggested that the POMC neurons, by themselves, aren’t the full counterpart to the AgRP neurons,” says lead author Henning Fenselau, PhD, a postdoctoral fellow in Lowell’s laboratory at BIDMC. “We hypothesized that an important but unknown neural component of the satiety system was missing from the current models.”

What’s more, because the team was looking for neurons that would suppress eating quickly, they narrowed their search for ones that release the fast-acting, excitatory neurotransmitter called glutamate. In the current paper, Lowell and colleagues investigated a third subset of neurons, Vglut2, the function of which was previously unknown.

In a series of experiments, Lowell and colleagues used optogenetics (the use of light to activate genetically modified neurons) and chemogenetics (the use of molecules to activate targeted neurons) to manipulate specific neurons to determine their roles in feeding behavior. First, the team demonstrated that, unlike POMC neurons, Vglut2 neurons could in fact rapidly suppress feeding behavior in mice. When the researchers chemically stimulated the neurons in question, it markedly decreased eating. When they inhibited the Vglut2 neurons, eating increased.

They also found that all three types of neurons—the hunger-promoting AgRP neurons and the two satiety-promoting neurons, Vglut2 neurons and POMC neurons—interact in the same circuit. All three converge downstream in a site in the hypothalamus known to suppress hunger, the subject of previous research by Lowell and colleagues. AgRP neurons inhibit activity in this downstream site, causing hunger, while the rapidly acting Vglut2 neurons excite it, suppressing hunger. The third member of this circuit, POMC neurons, indirectly decrease hunger by releasing a hormone that bolsters Vglut2 neurons’ ability to suppress hunger.

“We think this is very important because it may be one explanation why individuals lacking POMC genes become extremely obese, even if those neurons by themselves don’t directly promote satiety,” Fenselau says. “Without POMC, the Vglut2 neurons are ineffective in stimulating the downstream hypothalamic site. You need both POMC neurons and Vglut2 neurons for the satiety mechanism to work properly.”

Finally, the team sequenced the genes expressed by this subset of neurons and found they possess receptors for the hormone oxytocin. Known to play a role in social bonding, oxytocin is linked to feelings of contentment and is already being investigated for its potential as a satiety-inducing weight loss medication. “Our findings could definitely explain why oxytocin is effective in satiety,” Fenselau says.

— Source: Beth Israel Deaconess Medical Center