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Gastroenterology. 2017 May;152(7):1638-1646. doi: 10.1053/j.gastro.2016.12.051. Epub 2017 Feb 10.

Adolescent Obesity and Insulin Resistance: Roles of Ectopic Fat Accumulation and Adipose Inflammation.

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Department of Pediatric Endocrinology, Yale University School of Medicine, New Haven, Connecticut. Electronic address:
Department of Internal Medicine, Endocrinology, Yale University School of Medicine, New Haven, Connecticut.
The Jackson Laboratory, Farmington, Connecticut.


As a consequence of the global rise in the prevalence of adolescent obesity, an unprecedented phenomenon of type 2 diabetes has emerged in pediatrics. At the heart of the development of type 2 diabetes lies a key metabolic derangement: insulin resistance (IR). Despite the widespread occurrence of IR affecting an unmeasurable number of youths worldwide, its pathogenesis remains elusive. IR in obese youth is a complex phenomenon that defies explanation by a single pathway. In this review we first describe recent data on the prevalence, severity, and racial/ethnic differences in pediatric obesity. We follow by elucidating the initiating events associated with the onset of IR, and describe a distinct "endophenotype" in obese adolescents characterized by a thin superficial layer of abdominal subcutaneous adipose tissue, increased visceral adipose tissue, marked IR, dyslipidemia, and fatty liver. Further, we provide evidence for the cellular and molecular mechanisms associated with this peculiar endophenotype and its relations to IR in the obese adolescent.


Adipose Tissue Distribution; Adipose Tissue Inflammation; Childhood and Adolescent Obesity; Fatty Liver; Inflammasome; Resistance

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