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is characterized as resulting in either: “sick fat disease” (adiposopathy) or “fat mass disease.”
Fat mass disease occurs when abnormal
physical forces from enlarged adipose tissue
organ causes damage to other body tissues, such
as biomechanical stress on weight-bearing joints,
immobility, and tissue compression and friction.
Sick fat disease or adiposopathy, on the
other hand, occurs when adipocyte and/
or adipose tissue result in endocrine and
immune derangements contribute to metabolic
disease. This applies not only to atherosclerotic
cardiovascular disease (ASCVD), but also to
ASCVD risk factors. For instance, an increased
accumulation of dysfunctional adipose tissue
around the vasculature or around the heart
may well lead to peripheral inflammatory
signaling—this is sometimes known as the
“outside-in” atherogenic model. We are perhaps
more familiar with the “inside-in” atherogenic
model, wherein atherogenic lipoprotein particles
in the circulation contribute to atheroma and
plaque, generating an inflammatory response
that may result in plaque rupture, thrombosis,
and acute event. But the outside-in phenomenon
also might be applicable as well, wherein the
adipose tissue transmits these pro-inflammatory
responses from the outside of the vessel to the
inside of the vessel, which directly contributes to
atherogenesis and ASCVD progression.
But as you said, in addition to these direct
effects, indirect mechanisms are also in play.
When peripheral subcutaneous adipose tissue is
not able to undergo adequate adipogenesis (i.e.,
the process by which fat cells differentiate from
overflow may also result in increased fat
accumulation around blood vessels, heart, and
in the visceral region—which helps explain why
an increase in central obesity is a marker of not
only global adipose tissue dysfunction, but also a
marker for increased ASCVD risk.
Increased blood pressure is a prime example
of the adverse metabolic consequences of
adiposopathy. An increase in body fat may
increase leptin and insulin levels, both of
which may contribute to increased adrenergic
responses leading to increased blood pressure.
Other potential mechanisms helping to explain
the increase in blood pressure so often found
in patients with overweight or obesity include:
onset of sleep apnea, compression of the renal
vessels and kidneys, increased renin-angiotensin
activity, increased corticoid release, increase
in endothelial vasoconstrictors, decrease
in endothelial dependent vasodilation, and
decreased B-type natriuretic peptide.
Regarding dyslipidemia, in 2013, a consensus
statement for the National Lipid Association
specifically identified endocrine factors,
immune factors, lipids and apolipoproteins,
transfer proteins, biological transporters, and
cellular receptors as factors that contribute to
dyslipidemia in the presence of dysfunctional
adipose tissue. The end result is the characteristic
dyslipidemia we so often encounter in
clinical practice, which is marked by elevated
triglycerides, triglyceride-rich lipoproteins,
lipoprotein remnants, atherogenic particle
numbers, and increased proportion of small dense
low-density lipoprotein cholesterol particles.
“While most people probably recognize
obesity as a disease, many clinicians have
received inadequate education regarding the
pathogenic potential of adipose tissue.”
—Harold E. Bays, MD
preadipocytes to adipocytes), existing adipocytes
may undergo hypertrophy. Hypertrophy may lead
to fat cell endoplasmic reticulum dysfunction,
mitochondrial dysfunction, and a multitude
of endocrinopathies and immunopathies. The
inability to adequately store excess energy in
peripheral subcutaneous adipose tissue results
in energy overflow, increasing fat deposition in
the form of free fatty acids to the liver, pancreas,
and the heart, which may be “lipotoxic.” Energy
CardioSource.org/CSWN
With regard to glucose, an increase in
circulating fatty acids may result in the lipotoxicity
previously described, which may contribute to
insulin resistance in the liver and muscle, as well
as possibly suppressed insulin secretion from the
pancreas. Added to the various immunopathies
and endocrinopathies from dysfunctional adipose
tissue, it’s no wonder why a patient who gains
body fat develops hyperglycemia, if not type II
diabetes mellitus itself.
Dr. Cannon: Right, there are so many more nuances concerning obesity’s impact on cardiovascular
health than just saying to a patient, “You’re gaining
weight, your blood pressure is a little higher, and
your cholesterol is a little off.”
Dr. Bays: Exactly. Because body fat has historically
been considered mainly an energy sto