Emilio Antonio Francischetti
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Rômulo Sperduto Dezonne
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Cláudia Maria Pereira
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Cyro José de Moraes Martins
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Bruno Miguel Jorge Celoria
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...
AbstractIn 2016, the World Health Organization estimated that more than 1.9 billion
adults were overweight or obese. This impressive number shows that weight excess
is pandemic. Overweight and obesity are closely associated with a high risk of
comorbidities, such as insulin resistance and its most important outcomes,
including metabolic syndrome, type 2 diabetes mellitus, and cardiovascular
disease. Adiponectin has emerged as a salutary adipocytokine, with
insulin-sensitizing, anti-inflammatory, and cardiovascular protective
properties. However, under metabolically unfavorable conditions, visceral
adipose tissue-derived inflammatory cytokines might reduce the transcription of
the adiponectin gene and consequently its circulating levels. Low circulating
levels of adiponectin are negatively associated with various conditions, such as
insulin resistance, type 2 diabetes mellitus, metabolic syndrome, and
cardiovascular disease. In contrast, several recent clinical trials and
meta-analyses have reported high circulating adiponectin levels positively
associated with cardiovascular mortality and all-cause mortality. These results
are biologically intriguing and counterintuitive, and came to be termed
“the adiponectin paradox”. Adiponectin paradox is frequently
associated with adiponectin resistance, a concept related with the
downregulation of adiponectin receptors in insulin-resistant states. We review
this contradiction between the apparent role of adiponectin as a health promoter
and the recent evidence from Mendelian randomization studies indicating that
circulating adiponectin levels are an unexpected predictor of increased
morbidity and mortality rates in several clinical conditions. We also critically
review the therapeutic perspective of synthetic peptide adiponectin receptors
agonist that has been postulated as a promising alternative for the treatment of
metabolic syndrome and type 2 diabetes mellitus.
Insights Into the Controversial Aspects of Adiponectin in
Cardiometabolic Disorders
