Ceramides are a natural part of every cell.
They're one of the many, many types of fat or lipid that we have in all our
cells and we need ceramide, but the problem in our society is that
we have too much of it, but what we determined was that as ceramide over-
accumulates in the muscle cell of the person gaining weight, it starts to
pull these mitocondria apart and what was once a nice, connected network is now
individual, distinct little mitochondria and that's important
because those mitochondria don't work as well. So metabolic rate has been reduced in
the muscle from these obese individuals. So because we know ceramide is a source of metabolic problems, such as insulin resistance, if we could find a way to
prevent your body from accumulating ceramide, we could maybe in turn ameliorate or our solve some of those problems. In these animals that were experiencing this sort of metabolic stress, we were giving
them high-fat, high-sugar diet, and that's this perfect storm of weight gain. When we found when we
inhibited ceramide, even though they were
getting that same diet, that same high-fat, high-sugar diet, we found that the mitochondria stayed big, they stayed connected, and as a result they were resistant to
obesity. We couldn't get them fat and we couldn't
make them diabetic. In humans, perhaps this suggests that there is room to discover novel therapies where we can
inhibit the production of ceramide so that a muscle cell won't over-accumulate ceramide and, in the process, maintain healthy metabolic function. But independent of discovering a new drug is perhaps
just stressing again, not surprisingly, the importance of
lifestyle, where we found in our studies at a high-fat, high-sugar diet resulted in ceramide accumulation or
over-accumulation in the muscle. Also exercise has been found to
reduce ceramide level, so as much as people don't want to hear it,
maybe a drug will come out someday that would prevent ceramide accumulation in humans, but importantly, even now, diet and exercise are known to be
important regulators.
