Study identifies a hormone that may hinder weight loss

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By Tim Newman  


Fact checked by Isabel Godfrey

A series of experiments in
mice demonstrates that a well-known hormone might have a previously
unidentified role in the metabolic response to energy restriction during weight
loss.
Scientists have known about
growth hormone (GH) for several decades. It plays a role in bone growth and is
particularly important as our bodies grow.
It also helps maintain organs
and tissues as we go through our adult lives.
However, researchers at the
University of São Paulo in Brazil have found an entirely new and unexpected
role for GH: It appears to play a part in energy conservation during weight
loss.
José Donato Junior and his
team published their findings in the journal Nature Communications.
When an animal’s food intake
becomes restricted, its body responds by conserving energy.
This mechanism is important
because, in the wild, if an animal is having difficulty finding food, the body
needs to save as much energy as possible.
However, this is part of the
reason why it is incredibly difficult to prevent weight from returning after
dieting. For many years, researchers have tried to zero in on why this might be
the case.

Hormones and weight loss

Scientists already know that a
hormone called leptin plays a part in the body’s response to weight loss. Fat
cells produce leptin, which inhibits hunger. When we lose weight, levels of
leptin in the bloodstream drop, making us more likely to feel hungry.
Some people can develop leptin
resistance, which means that they no longer respond to the hormone and,
consequently, feel hungry more often.
As Donato explains,
“Leptin has hitherto been considered the main hormone that acts to
conserve energy when we’re hungry.”
However, despite scientists’
growing understanding of leptin, it has not led to any successful weight-loss
interventions. The most recent study asks whether GH might be one of the
missing pieces of the puzzle.
“GH receptors are found
in large quantities in muscle and tissue, in the liver, and in organs directly
involved in growth metabolism,” says Donato, “but we found that the
brain is also full of GH receptors. This is entirely new.”
The scientists demonstrated
that leptin levels decrease in response to a restriction in caloric intake,
while levels of GH increase.
Where are the GH receptors?

The scientists found an
abundance of GH receptors in the hypothalamus. The hypothalamus regulates the
autonomic nervous system, which is the arm of the nervous system that controls
automatic functions, such as breathing and digestion.
The hypothalamus also plays an
important role in controlling energy homeostasis — the regulation of energy
expenditure and food intake.
In the hypothalamus, a small
collection of neurons produce agouti-related protein (AgRP). When these neurons
release AgRP into the body, appetite increases, and the body holds onto its
energy stores more tightly.
The scientists found that GH
receptors in the hypothalamus activate these neurons, triggering the release of
AgRP.
To understand what influence
GH might be having on AgRP neurons, the researchers genetically engineered a
strain of mice that lacked the AgRP-specific GH receptor (AgRP GHR KO mice).
In a series of experiments,
the scientists deprived mice of food and assessed their energy expenditure.
The control mice, which still
had the GH receptor, responded to restricted food intake as expected by
reducing their energy expenditure.
However, in the AgRP GHR KO
mice, the drop in energy expenditure was much less pronounced. Consequently,
these mice lost more weight over the course of the study. The loss of
energy-dense fatty tissue accounted for most of this weight decrease, but there
was also some loss of lean mass, which includes muscle, bone, organs, tendons, and
fluids.
Blocking growth hormone

In a separate experiment, the
researchers used mice that they had not engineered to lack the GH receptor.
This time, they used a drug called pegvisomant that blocks GH receptors
instead.
Once again, with food
deprivation, the energy expenditure of these mice decreased significantly less
than it did in mice that had not received pegvisomant.
“GH is not only involved
in growth metabolism but, above all, influences the metabolic responses that
conserve energy when we’re hungry or on a diet,” concludes Donato.
“In other words, we
discovered that weight loss triggers an increase in hypothalamus GH levels,
which activates the AgRP neurons, making weight loss harder and intensifying
the sense of hunger. That’s precisely the same function leptin performs.”
Lead author José Donato Junior

The authors conclude that GH
does not appear to play a significant role in energy balance when the animals
have adequate access to food. Instead, it “signals energy deficiency to
the brain, triggering neuroendocrine responses to conserve body energy
stores.”
Donato explains that because
conserving energy is so important for survival, animals appear to have evolved
two separate systems.
The authors also hypothesize
that this might be why weight-loss interventions based solely on leptin are
ineffective — they are only addressing part of the mechanism.
In the future, the authors
believe that compounds that target GH receptors could “represent a
promising approach to facilitate weight loss and improve the efficacy of
obesity treatments.”





SOURCE: MEDICAL NEWS TODAY

Kayode Ojo
Kayode Emmanuel Ojo is the Co-Founder and Managing Director at SHEFFA Limited. He is presently studying Computer Science at the National Open University, Victoria Island, Lagos.