ISSN 1022-7954, Russian Journal of Genetics, 2008, Vol. 44, No. 10, pp. 1160–1175. © Pleiades Publishing, Inc., 2008.
Original Russian Text © A.V. Baranova, 2008, published in Genetika, 2008, Vol. 44, No. 10, pp. 1338–1355.
CLINICAL SIGNS OF THE METABOLIC
SYNDROME AND GENETIC CONTRIBUTION
TO ITS COMPONENTS
The metabolic syndrome (MS) was described as an
independent disorder in 1988 . MS is clinically man-
ifested as a combination of various interrelated signs,
including central obesity, insulin resistance (IR), ele-
vated blood pressure, a high level of blood triglycer-
ides, and a decrease in high density lipoproteins (HDL).
MS facilitates the development of secondary complica-
tions of central obesity, in particular, CVDs and type II
diabetes. In addition, MS contributes to the etiology of
obstructive sleep apnea, erection problems, polycystic
ovary syndrome, and various malignancies.
The list of MS-associated disorders was recently
supplemented with nonalcoholic fatty liver disease
(NAFLD), including nonalcoholic steatohepatitis
(NASH), the most aggressive NAFLD form that often
leads to liver ﬁbrosis and cirrhosis. The epidemiology,
pathogenesis, and therapy of NAFLD follow the same
trends as the other MS-associated disorders . IR acts
as a key link that associated NAFLD with MS .
Many MS parameters are inherited; i.e., they are
determined by certain alleles occurring in the individ-
ual genotype. The contribution of the genetic compo-
nent was estimated at 68% for total body mass and
body mass index (BMI), 63% for serum HDL, 55% for
serum leptin, 53% for percent body fat and serum cho-
lesterol, 51% for serum insulin and regular eating unre-
lated to hunger, 43% for serum triglycerides, 40% for
waist circumference, 38% for diastolic blood pressure,
and 28% for insulin sensitivity [4–7]. In total, the inher-
itance coefﬁcient of MS IS 0.38 .
In spite of the obvious signiﬁcance of MS in the
morbidity structure, the diagnostic criteria of MS are
far from perfect. Similar, but not identical, criteria were
proposed for MS diagnosis by the World Health Orga-
nization (WHO); US National Expert Panel on Detec-
tion, Evaluation, and Treatment of High Blood Choles-
terol (ATPIII); International Diabetes Federation
(IDF); European Group for the study of Insulin Resis-
tance (EGIR); and American College of Endocrinology.
In 2005, the multiplicity of nonidentical clinical deﬁni-
tions of MS was detailed in a joint statement of the Amer-
ican Diabetes Association (ADA) and European Associa-
tion for the Study of Diabetes (EASD) . As emphasized
in the statement and many other works, additional criteria
should be used to diagnose MS. One of the possible crite-
ria is the serum proﬁle of soluble proteins synthesized and
secreted by adipose tissue (AT).
STRUCTURE OF ADIPOSE TISSUE
AND GENETIC FACTORS AFFECTING
Adult AT consists mostly of subcutaneous fat and
visceral fat, located in the abdominal cavity. These two
adipose compartments substantially differ in metabo-
lism and secretion. In particular, visceral AT adsorbs
Adipokine Genetics: Unbalanced Protein Secretion by Human
Adipose Tissue as a Cause of the Metabolic Syndrome
A. V. Baranova
Medical Genetics Research Center, Russian Academy of Medical Sciences, Moscow, 115478 Russia
Molecular and Microbiology Department, College of Sciences, George Mason University, Fairfax, VA 22003, USA;
Received July 10, 2007; in ﬁnal form, May 12, 2008
—Subcutaneous and visceral adipose compartments act, not only as fatty acid depots, but also as
active endocrine organs that undergo hyperplastic changes and signiﬁcantly enhance their function in obesity.
Adipokines and other proteins secreted by both adipocytes and stromal cells play a central role in peripheral
insulin resistance and the metabolic syndrome (MS). Minor alleles of the adipokine genes substantially contrib-
ute to MS. The most important consequence of MS is low-level systemic inﬂammation supported by adipose-
speciﬁc synthesis of proinﬂammatory soluble molecules. Proinﬂammatory signals are secreted into the blood-
stream and spread to peripheral tissues that express their receptors. The signals provided by adipose tissue stim-
ulate the development of secondary complications of MS, including cardiovascular disorders (CVDs) and non-
alcoholic fatty liver disease. The review describes the physiological effects of adiponectin, leptin, resistin, vis-
fatin, and apelin and the inﬂuence of the minor alleles of the adipokine genes on the development of the
secondary complications of MS.
REVIEWS AND THEORETICAL