Sun Exposure and Fat Loss
Sun Exposure and
Fat Loss
“Eureka!” is heard as scientists
uncover new discoveries, the cry accompanied by a cartoon light bulb appearing
overhead. If that cartoon scene holds a clue to fat loss, it may be the light
cast by the bulb. Insane, right? Surely fat loss is not as simple as upgrading
from 60 to 75 watts? Of course it isn’t, but there is a body of evidence
suggesting that fat loss may be related to light exposure, more specifically,
sun exposure.
Understanding the process involved is
at first complex, but with a little effort, it becomes clear. In fact, don’t be
surprised if you need to read this article two or three times to fully
understand it, as it deals with true cutting-edge science. The process likely
evolved eons ago, when man was just learning to walk upright and considered
fire to be a message from the gods. Before the advent of air-conditioning,
forced-air furnaces and grocery stores, mankind responded to the changes in
season just the way animals continue to do today.
The only measure of time available to
primitive man was the length of the day, with shorter days announcing the
coming of winter and a period of famine (starvation). As the days lengthened,
warmer weather approached and food became more readily available. Man responded
to the coming of winter by storing fat and burning fewer calories, while summer
required him to shed those excess pounds to hunt and gather without becoming
prey to carnivorous predators. The question arises: How did the sun signal
primitive man to store fat for the winter and shed fat in the summer?
Pieces of a Puzzle
The path from sunshine to fat loss is
like a puzzle in which all the pieces have to be identified and put together to
form the picture. A close look at the pieces will show how they fit together
and then the picture will be clear.
The sun is a source of ultraviolet (UV)
rays, which cause oxidative stress (molecular injury) on the skin cell membrane
and can lead to skin damage or cancer.1,2 The body has a mechanism
for protecting against UV-caused skin damage by increasing the amount of a
protective pigment called eumelanin.3,4
Eumelanin pigment builds up in the skin following UV exposure; this process is
easily recognized by every sunbather as “tanning.” Sunshine and tanning seems
like a simple cause-and-effect relationship, but there are a number of steps
involved before the appearance of the first freckle. Even more incredible is
the far-reaching impact of the UV-tanning cascade on other tissues, including
fat cells and the brain.
When UV rays strike the skin cell
surface, they turn on certain genes within the cell’s DNA.4,5 These
genes produce a pre-prohormone called proopiomelancortin
(POMC).4,5 POMC is broken down to smaller fragments, including a
class of hormones called melanocortins.4-8
Specific melanocortins, including µ-MSH (melanocyte stimulating hormone)
stimulates the actual eumelanin production, resulting in a tan.4,9
Not surprisingly, eumelanin is an antioxidant, protecting against further
UV-related damage, which explains why the body responds with a tan when
assaulted by UV rays.3
Sun Exposure and Fat Loss
This describes how and why the sun tans
the skin, but not how sun exposure causes fat loss. The hormones involved in
the body’s response to sun exposure, the melanocortins, are players in other
tissues besides the skin.
A great deal of attention has been paid to a
recent discovery in fat cell metabolism— a hormone known as leptin. Leptin is
produced by the fat cells in abundance when fat content is high, and leptin
levels drop as body fat is
lost.10-12 Leptin, when administered as a drug,
causes normal humans and rats to eat less and burn more calories.10-12
However, attempts to turn leptin into a fat loss drug have failed because most
obese people do not respond to leptin treatment. This is called leptin
resistance.10,12,13 Leptin research has continued and scientists
have discovered that leptin acts upon certain areas of the brain, stimulating
the production of— yup— melanocortins.10-12,14
These melanocortins, the same hormones
produced by the skin, suppress the appetite centers in the brain, decreasing
the amount of food eaten and causing weight loss.10,12 Animal
experiments injecting melanocortins directly into the brain have proven the
actions and effectiveness of these hormones.10,15,16 However, there
are always checks and balances in the body, and the leptin-melanocortin system
is no exception. A separate hormone, called agouti,
is also present in the same areas of the brain and competes with the
melanocortins.7,10,11,15-18 When the balance is tipped towards
agouti, the subject becomes hungry, increasing food intake and gaining weight.10,11,14,16,18
So, leptin increases when the body gets fatter, causing the brain to produce
melanocortins, which suppress the appetite. To avoid losing weight too rapidly,
a counter-hormone called agouti competes with the melanocortins when body fat
drops, restoring the appetite.
Research has shown that melanocortins
injected into the body affect the brain and weight gain, just like they do when
injected directly into the brain.6,8,13,19-21 This suggests that
melanocortins produced in the skin may circulate through the bloodstream and
affect the brain and other tissues.
Interestingly, the same hormones that
cause tanning also affect the appetite, but fat loss involves more than
controlling the appetite. Melanocortins and agouti, the same hormones competing
to control the appetite in the brain, both act on the fat cell.6,17,22-24
Fat cells contain receptors that respond to agouti by increasing the
concentration of calcium in the fat cell.22,23 Increased calcium
inside the fat cell promotes lipogenic process and enzymes, creating more fat
inside the cell, decreasing fat loss.22,23,25,26 When the balance
outside the cell favors melanocortins, calcium is prohibited from entering the
fat cell and stored fat is broken down and released, to be burned as fuel by
the body.6,23,24
The Vitamin D Factor
The actions of melanocortins and agouti on the
fat cell appear to involve modifying the effects of vitamin D. Vitamin D is
created in the skin, in a reaction involving sun exposure.25 It is sensible that the skin would generate
and release a messenger hormone (vitamin D is a steroid molecule) that acts
upon the fat cell. During winter, which would be anticipated by a shorter
period of daylight, fat would function both as a source for stored energy and
as a thermal insulator, protecting against the oncoming cold weather. During
the summer, an individual needs to shed the blanket of fat to be more mobile
and to improve heat loss. Failure to lose the stored fat would have put
primitive man at a disadvantage, making him slow and prone to heat exhaustion
when hunting or avoiding predators.
In addition to these effects, it
appears that melanocortin is also able to increase the body’s metabolism,
increasing the rate at which calories are burned. Animal data suggest that in
the presence of melanocortins, uncoupling protein-3 is increased.13,15,19,20
Uncoupling proteins make the body less efficient, causing calories to be
released as heat, rather than used for energy production. Adding to the
metabolic increase is the effect of melanocortins on thyroid hormone release.
When exposed to melanocortins, the thyroid increases its output, further increasing
the body’s metabolism and fat burning rate. 26
A Potent Mechanism
So many pieces, but when put in place,
they describe a potent mechanism by which the body reacts to the anticipated
onset of famine (winter) and feasting (summer). Sunlight “irritates” the skin,
turning on a genetic sequence, creating melanocortins. These melanocortins
increase the skin’s pigment (eumelanin) but also circulate throughout the body,
possibly affecting other systems. Melanocortins have been shown to affect fat
storage and release, appetite and the metabolic rate of the entire body. Within
the brain, melanocortin production is influenced by the amount of fat stored by
the body, and appears to be involved in weight maintenance, even in the absence
of sunlight.
Apparently the process has not escaped
the attention of several pharmaceutical companies who have rushed to patent a
number of drugs that act like the naturally produced melanocortins.27-33
Much of the research is currently focused on the use of melanocortin-like drugs
to treat obesity7,21,27,34 and impotence28-38 (yes, it
increases erections too), in addition to the tanning effect, leading the press
to call these drugs “Barbie drugs” after the ever-beautiful BarbieÒ
Dolls.39
When considered as a whole, this evidence
would suggest that increasing sun exposure, sufficient to cause a tanning
response, may support fat loss efforts. Tanning might make dieting easier by
decreasing the appetite, reducing food intake and increasing the use of stored
fat for calories. The stored fat may be more readily released and burned as
fuel. Those who do not tan easily, such as redheads and those with fair skin,
are unlikely to benefit to the same degree.1,2,9,40,41
Tanning is not without risk, as skin
damage and cancerous changes increase with prolonged and excessive sun
exposure. It’s recommended that a skin cancer screen be performed prior to
tanning and if any skin lesions or changes are noted.
References
- Healy E, Flannagan N, et al. Melanocortin-1 receptor gene
and sun sensitivity in individuals without red hair. Lancet 2000 Mar 25;355(9209):1072-3.
- Rees JL, Healy E. Melanocortin
receptors, red hair, and skin cancer. J
Investig Dermatol Symp Proc 1997 Aug;2(1):94-8.
- Pawelek JM. Approaches to
increasing skin melanin with MSH analogs and synthetic melanins. Pigment Cell Res 2001
Jun;14(3):155-60.
- Slominski A, Wortsman J, et al. Corticotropin releasing
hormone and proopiomelanocortin involvement in the cutaneous response to
stress. Physiol Res 2000
Jul;80(3):979-1020.
- Suzuki I, Kato T, et al. Increase of
pro-opiomelanocortin mRNA prior to tyrosinase, tyrosinase-related
protein-1, dopachrome tautomerase, Pmel-17/gp100, and P-protein mRNA in
human skin after ultraviolet B irradiation. J Invest Dermatol 2002 Jan;118(1):73-8.
- Stephenson JS. Knockout Science:
chubby mice provide new insights into obesity. JAMA 1999 Oct 27;282(16):1507-8.
- MacNeil
DJ, Howard AD, et al. The role
of melanocortins in body weight regulation: opportunities for the
treatment of obesity. Eur J
Pharmacol 2002 Apr 12;440(2-3):141-57.
- Yaswen L, Diehl N, et al. Obesity in the mouse model
of pro-opiomelanocortin deficiency
responds to peripheral melanocortin. Nat
Med 1999 Sep;5(9):1066-70.
- Suzuki I, Im S, et al. Participation of the
melanocortin-1 receptor in the UV control of pigmentation. J Investig Dermatol Symp Proc 1999
Sep;4(1):29-34.
- Marks DL, Cone RD. Central
melanocortins and the regulation of weight during acute and chronic
disease. Recent Prog Horm Res
2001;56:359-75.
- Zemel MB. Agouti/melanocortin
interactions with leptin pathways in obesity. Nutr Rev 1998 Sep;56(9):271-4.
- Lu H, Buison A, et al. Leptin resistance in obesity
is characterized by decreased sensitivity to proopiomelanocortin products.
Peptides 2000
Oct;21(10):1479-85.
- Cettour-Rose P, Rohner-Jeanrenaud
F. The leptin-like effects of 3-d peripheral administration of a
melanocortin agonist are more marked in genetically obese Zucker (fa/fa)
than in lean rats. Endocrinology
2002 Jun;143(6):2277-83.
- Adage T, Scheurink AJ, et al. Hypothalamic, metabolic, and
behavioral responses to pharmacological inhibition of CNS melanocortin
signaling in rats. J Neurosci
2001 May 15;21(10):3639-45.
- Hwa JJ, Ghibaudi L, et al. Central melanocortin system
modulates energy intake and expenditure of obese and lean Zucker rats. Am J Physiol Regul Integr Comp Physiol
2001 Aug;281(2):R444-51.
- Fan W, Boston BA, et al. Role of melanocortinergic
neurons in feeding and the agouti obesity syndrome. Nature 1997 Jan 9;385(6612):165-8.
- Voisey J, van Daal A. Agouti: from
mouse to man, from skin to fat. Pigment
Cell Res 2002 Feb;15(1):10-8.
- Ollman MM, Wilson BD, et al. Antagonism of central
melanocortin receptors in vitro and in vivo by agouti-related protein. Science 1997 Oct 3;278(5335):135-8.
- Chen AS, Metzger JM, et al. Role of the melanocortin-4
receptor in metabolic rate and food intake in mice. Transgenic Res 2000 Apr;9(2):145-54.
- Pierroz DD, Ziotopoulou M, et al. Effects of acute and chronic
administration of the melanocortin agonist MTII in mice with diet-induced
obesity. Diabetes 2002
May;51(5):1337-45.
- Dhillo WS, Bloom SR. Hypothalamic
peptides as drug targets for obesity. Curr
Opin Pharmacol 2001 Dec;1(6):651-5.
- Kim JH, Kiefer LL, et al. Agouti regulation of
intracellular calcium: role of melanocortin receptors. Am J Physiol 1997 Mar;272(3 Pt
1):E379-84.
- Xue
B, Moustaid N, et al. The agouti
gene product inhibits lipolysis in human adipocytes via a Ca+2 dependent
mechanism. FASEB J 1998
Oct;12(13):1391-6.
24
Boston BA. The role of melanocortins in
adipocyte function. Ann N Y Acad Sci
1999 Oct 20;885:75-84.
25
Ganong WF. Review of Medical Physiology, 19th
ed. – Hormonal control of calcium metabolism & the physiology of bone
(chapter 21). Lange Medical Books/McGraw-Hill, New York, 1999:371-2.
26
Krotkiewski
M. Thyroid hormones in the pathogenesis and treatment of obesity. Eur J Pharmacol 2002 Apr
12;440(2-3):85-98.
27
Cone
RD, Fan W, et al. US Patent
6,476,187. Methods and reagents for discovering and using mammalian
melanocortin receptor agonists and antagonists to modulate feeding behavior in
animals. 2002 November 5.
28
Bakshi
RK, Nargund RP, et al. US Patent
6,376,509. Melanocortin receptor agonists. 2002 April 23.
29
Nargund
RP, Ye Z, et al. US Patent 6,410,548.
Spiropiperidine derivatives as melanocortin receptor agonists. 2002 June 25.
30
Hadcock
JR, Swick AG. US Patent 6,451,783. Treatments for obesity and methods for
identifying compounds useful for treating obesity. 2002 September 17.
31
Palucki
B, Barakat K, et al. US Patent
6,458,790. Substituted piperidines as melanocortin receptor agonists. 2002
October 1.
32
Palucki
B, Nargund R. US Patent 6,472,398. Spiropiperidine derivatives as melanocortin
receptor agonists. 2002 October 29.
33
Lee
F, Huszar D, et al. US Patent
5,932,779. Screening methods for compounds useful in the regulation of body
weight. 1999 August 3.
34
Anonymous.
Press Release. Competitve Technologies client to be interviewed on sun-less
tanning and sexual dysfunction technology. 2002 July 29. Available through http://biz.yahoo.com/pz/020729/30014.html
accessed February 3, 2003.
35
Vemulapalli
R, Kurowski S, et al. Activation of
central melanocortin receptors by MT-II increases cavernosal pressure in
rabbits by the neuronal release of NO. Br
J Pharmacol 2001 Dec;134(8):1705-10.
36
Wesselis
H, Grainek D, et al. Effect of an
alpha-melanocyte stimulating hormone analog on penile erection and sexual
desire in men with organic erectile dysfunction. Urology 2000 Oct 1;56(4):641-6.
37
Wesselis
H, Levine N, et al. Melanocortin
receptor agonists, penile erection, and sexual motivation: human studies with
melanotan II. Int J Impot Res 2000
Oct;12 Suppl 4:S74-9.
38
Anonymous.
Press Release. Competitive Technologies’ licensee reports PT-141 data for
males. 2003 January 23. Available through http://biz.yahoo.com/prnews/030123/nyth158_1.html
accessed February 3, 2003.
39
Usborne
D. Paradise in a pill? The Independent. 2002 July 31. Available through http://news.independent.co.uk/world/australia/story.jsp?story=319949
accessed February 3, 2003.
40
Flanagan
N, Ray AJ, et al. The relation
between melanocortin 1 receptor genotype and experimentally assessed
ultraviolet radiation sensitivity. J
Invest Dermatol 2001 Nov;117(5):1314-7.
41
Sturm
RA. Skin colour and skin cancer – MC1R, the genetic link. Melanoma Res 2002 Sep;12(5):405-16.