2015-06-29

low melatonin may cause #obesity

5.14: news.health/low melatonin may cause obesity:
summary:
. there are 2 types of body fat:
white used for energy storage,
and brown for generating heat .
. sedentary people on high-calorie diets
can still remain thin because calories are
being burned for generating heat
by activation of their brown fat .
. being exposed to shorter periods of darkness
due to increasing use of artificial lights
may cause reduced levels of melatonin,
and may result in reduced activity of brown fat
resulting in an increased risk of obesity .
. melatonin also has other metabolic effects
that contribute to prevention of obesity .
The reduction in melatonin production,
as during aging, shift-work
or illuminated environments during the night,
induces insulin resistance, glucose intolerance,
and metabolic circadian disorganization
leading to obesity.

Transl Res. 2015:
In humans, 2 different types of adipose tissue
coexist: white adipose tissue (WAT)
and brown adipose tissue (BAT).
WAT is involved in energy storage,
whereas BAT is involved in energy expenditure.
Increased amounts of WAT may contribute to
the development of metabolic disorders,
such as obesity-associated type 2 diabetes mellitus
and cardiovascular diseases. In contrast,
the thermogenic function of BAT allows
high consumption of fatty acids
because of the activity of uncoupling protein 1
in the internal mitochondrial membrane.
[ uncoupling protein 1:
Thermogenin (called uncoupling protein by its discoverers
and now known as uncoupling protein 1, or UCP1)
is found in the mitochondria of brown adipose tissue (BAT).
It is used to generate heat by non-shivering thermogenesis.
] Interestingly,
obesity reduction and insulin sensitization
have been achieved by BAT activation-regeneration
in animal models.

Obes Rev. 2011:
. a substantial amount of
functional brown adipose tissue (BAT)
is retained in adult humans;
BAT disposes of extra energy via generation of heat .
. melatonin increases recruitment of brown adipocytes
and elevates their metabolic activity in some mammals
perhaps also in humans.

PNAS May 11, 2015:
Prolonged daily light exposure increases body fat mass
through attenuation of BAT (brown adipose tissue) activity.
. noradrenergic activation of brown adipose tissue
was reduced by increasing light exposure;
. prolonged day length (decreasing darkness length)
decreases sympathetic input into BAT,
reducing β3-adrenergic intracellular signaling;
and, decreased the BAT's metabolism of
fatty acids and glucose .
. impaired BAT activity is an important mediator
in the association between
disturbed circadian rhythm and adiposity;
making it likely that activation of BAT
may overcome the adverse metabolic consequences
of disturbed circadian rhythmicity.

sciencenews.org:
. mice exposed to longer periods of light
gained fat because their brown fat
wasn't working efficiently.

J Pineal Res. 2014:
. melatonin has anti-obesogenic effects;
melatonin is necessary for the proper
synthesis, secretion, and action of insulin.
Melatonin acts by regulating GLUT4 expression
and/or triggering, via its G-protein-coupled membrane receptors,
the phosphorylation of the insulin receptor
and its intracellular substrates
mobilizing the insulin-signaling pathway.
Melatonin is responsible, in part, for
the daily distribution of metabolic processes
so that the activity/feeding phase of the day
is associated with high insulin sensitivity,
and the rest/fasting is synchronized to the
insulin-resistant metabolic phase of the day.
Furthermore, melatonin is responsible for the
establishment of an adequate energy balance
mainly by directly regulating the energy expenditure
through the activation of brown adipose tissue
and turning white adipose tissue into BAT.
The reduction in melatonin production,
as during aging, shift-work
or illuminated environments during the night,
induces insulin resistance, glucose intolerance,
and metabolic circadian disorganization
leading to obesity.

J Pineal Res. 2013:
. megadosing Melatonin induces browning of
inguinal[in-the-groin] white adipose tissue
in Zucker diabetic fatty rats.
Melatonin limits obesity in rodents
without affecting food intake and activity,
suggesting a thermogenic effect.
Identification of brown fat (beige/brite)
in white adipose tissue (WAT)
prompted us to investigate whether
melatonin is a brown-fat inducer.
. the Zücker diabetic fatty (ZDF) rat
is a model of obesity-related type 2 diabetes
and a strain in which melatonin reduces obesity
and improves their metabolic profiles.
At 5 wk of age, ZDF rats and lean littermates (ZL)
were subdivided into two groups,
each composed of four rats:
control and those treated with oral melatonin
in the drinking water (10 mg/kg/day) for 6 wk.
Melatonin induced browning of WAT
in both ZDF and ZL rats.
Melatonin increased temperature by 1.36 in ZL
and by 0.55 in ZDF rats .
Melatonin increased the amounts of thermogenic proteins,
uncoupling protein 1 (UCP1) (by ~2-fold, P < 0.01)
and PGC-1α (by 25%, P < 0.05)
in extracts from beige inguinal areas in ZL rats.
Melatonin also induced measurable amounts of UCP1
and stimulated by approx'ly 2-fold
the levels of PGC-1α in ZDF animals.
These results demonstrate that chronic oral melatonin
drives WAT into a brown-fat-like function in ZDF rats.
This may contribute to melatonin's control of body weight
and its metabolic benefits.