December 11, 2012
WEST LAFAYETTE, Ind. – A
steak slapped onto a hot barbecue will leave the meat with black grill lines
that add flavor and aroma, but the chemicals contained in charred, seared and
fried foods may over time kick-start the body’s ability to add new fat cells
and increase the risk of age-related diseases, a Purdue University study shows.
Over time, the human body
shuts down the ability of young fat cells to mature and accumulate lipids. But
grilling, searing and frying create glycated proteins, which result from
proteins chemically bonding with sugar.
“When you put proteins
and sugars together at high temperatures, there is a chemical reaction, and
that creates flavor and texture, which we think of as good things,” said
Kee-Hong Kim, an assistant professor of food science. “Research suggests
that these glycated proteins are involved in age-related diseases like
Kim wanted to see whether
glycated proteins affect the speed at which precursor, or immature, fat cells
turn into mature fat cells. Using a cell culture, Kim saw no change in how
quickly those immature cells accumulated lipids, which is stored as fat in
cells, but he did notice something else.
“Older animals don’t
generally accumulate new fat cells. Those precursor cells lose their ability to
become mature as we age,” Kim said. “But
when exposed to glycated proteins, immature fat cells started to differentiate
and accumulate lipids like they would in a younger animal.
“When we continuously
consume glycated proteins we might turn on the ability of precursor cells to
mature,” said Kim, whose findings were published in the Journal of Biological Chemistry.
Kim found that the
byproducts of glycated proteins – advanced glycation end products, or AGEs –
interfere with cellular processes that should kill immature fat cells in older
animals. That means those animals, or people, may accumulate more fat cells
than they should, and those cells store compounds that can lead to inflammation
and certain types of diseases.
AGEs interact with a protein
called p53, which usually begins cell death and aging programs for immature fat
cells. With p53 disrupted, the immature fat cells survive and can accumulate
interesting that a single food component could contribute to a number of
diseases,” said Chih-Yu Chen, a doctoral student in Kim’s laboratory.
“This could cause people to think about their food preparation and diet
Kim is investigating the
relationship between obesity and a number of chronic illnesses such as
diabetes, cardiovascular disease and some types of cancer. He believes glycated
proteins may be a factor in some of those diseases.
“It’s not immediately
toxic, but if you’re exposed over a long period of time, some portions of the
glycated materials accumulate in the cells or tissues, and over time, that
contributes to inflammation and oxidative stress,” Kim said.
Next, Kim would like to
confirm his findings in an animal model. The Purdue Research Foundation, a
Ralph W. and Grace M. Showalter Research Trust Award, and Purdue startup funds
supported his work.
Writer: Brian Wallheimer,
765-496-2050, [email protected]
Sources: Kee-Hong Kim, 765-496-2330, [email protected]
Chih-Yu Chen, 765-496-3820, [email protected]
An Advanced Glycation End Products (AGEs)-The
Receptor for AGEs Axis Restores Adipogenic Potential of Senescent Preadipocytes
through Modulation of p53 Protein Function
Chih-Yu Chen, Allison Martorano Abell, Yang Soo Moon,
and Kee-Hong Kim
Impaired adipogenic potential of senescent
preadipocytes is a hallmark of adipose aging and aging-related adipose
dysfunction. While advanced glycation end products (AGEs) derived from both
foods and endogenous non-enzymatic glycation, and AGEs-associated signaling
pathways are known to play a key role in aging and its-related diseases, the
role of AGEs in adipose aging remains elusive. We show a novel pro-adipogenic
function of AGEs in replicative senescent preadipocytes and mouse embryonic
fibroblasts, as well as primary preadipocytes isolated from aged mice. Using
glycated bovine serum albumin (BSA) as a model protein of AGEs, we examined
that glycated BSA restores impaired adipogenic potential of senescent
preadipocytes in vitro and ex vivo. However, glycated BSA showed no
effect on adipogenesis in non-senescent preadipocytes. AGEs-induced the
receptor for AGEs (RAGE) expression is required for the pro-adipogenic function
of AGEs in senescent preadipocytes. This is through RAGE-dependent impairment
of p53 expression and p53
function in regulating p21
expression in senescent preadipocytes. We also observed a direct binding
between RAGE and p53 in senescent preadipocytes. Taken together, our findings
reveal a novel pro-adipogenic function of AGEs-RAGE axis in p53-regulated
adipogenesis of senescent preadipocytes, providing new insights into
aging-dependent adiposity by diet-driven and/or endogenous glycated proteins.