UCSC-MIRT Team projects(2 graduate
students, 4 undergraduates)
[Activities and Research in Argentina][Mexico][M.I.R.T. home]
Biomedical Relevance
In the US and other developed nations, excess caloric consumption and
lack of physical activity has lead to wide spread morbid obesity and the
concomitant rise in mortality and morbidity due to cardiovascular disease
including stoke and hypertension, diabetes and renal insufficiency, to name
but a few. Although these problems are present at all strata of the population
there is clear evidence that minority populations are disproportionately
afflicted to an alarming degree. In stark contrast, many d
eveloping countries
are poor and the population suffers from conditions ranging from malnutrition
to starvation. We do not pretend that our research will solve these problems,
but we do offer physiological research in a unique and dramatic animal model,
the elephant seal, that routinely endures the above nutritional conditions
during its life history yet suffers none of the pathology that would result
in other mammalian species, including humans. We are confident that these
studies will provide insights into the physiological mechanisms underlying
these extreme adaptations that may well be applicable to treatment and prevention
of related pathology in the humans.
Project 1. Obesity, Fasting metabolism, body composition, protein sparing
and the role of leptin in nutrition in elephant seals.
Except for the brief suckling period following birth, all elephant seals
would be classified as clinically obese by most mammalian standards, since
proportion of body fat remains in excess of 50% by mass throughout their
lifetime. Yet careful observation over more than a decade reveals no obvious
pathological consequences. We want to know why and how.
In stark contrast, while on land for annual reproduction and molting
activity elephant seals routinely fast entirely from food and water for
up to 3 months. Again, we have been unable to detect any pathological consequences
of these remarkable fasts. We want to more fully understand the biochemical
and physiological mechanisms underlying this extraordinary behavior.
Here we outline the studies designed to answer specific in this project
to be carried out by UCSC-MIRT research teams over the course of 3-4 seasons
at Punta Delgado. Virtually all of these studies will be conducted in newly
weaned seals that fast for 8-12 weeks before exiting the rookery for their
first trip to sea.
What is the elephant seal proximate body composition during prolonged
fasting? We will employ standard clinical methods, such as radio labeled
water dilution and sonography to measure these parameters.
Does the level of the newly discovered mammalian appetite regulatory
hormone, leptin, vary as the level body fat changes during the fast? We
will monitor the level of the hormone in the circulation in 12 animals over
the course of the entire fast.
What are the levels of protein turnover and catabolism in these animals
during the fast? Is body protein rigidly spared from oxidation during the
fast while being redistributed in the body? We will measure both urea formation
( proxy for catabolism) as well as amino acid incorporation and catabolism
to quantify these processes.
During this absolute fast is fat oxidation alone sufficient to supply
necessary water to support overall tissue homeostasis? Measurements of fat
oxidation and consequent metabolic water formation in 6-8 animals at various
stages of the fast will provide the required data to answer this question.
Are there any macroscopic, microscopic or biochemical pathologies in
the cardiovascular systems of adult elephant seals after a life time of
being "clinically obese? We will obtain tissue samples during autopsy
of several adult male and female elephant seals that die on land following
shark attacks as they approach the rookery each year. This natural predation
provides a wealth of fresh tissue to the investigators that would be otherwise
unavailable since none of our studies permit euthanasia.
Project 2 Regulation of Fluid and Electrolyte Homeostasis in Naturally
Fasting Elephant Seal Pups
Elephant seal pups routinely undergo a 10-12 week postweaning fast while
continuing normal mammalian development but no growth. Extended periods
of aphagia could potentially have deleterious consequences on fluid and
electrolyte homeostasis. However, previous studies have reported no such
alterations in fluid and electrolyte homeostasis in elephant seal pups during
their postweaning fast. Elephant seals have obviously developed the appropriate
physiological mechanisms that have allowed them to fast for such long periods,
however, these mechanisms remain largely undefined. Among the mechanisms
that must be employed are those that involve the conservation of water and
electrolytes.