Background: Body weight homeostasis and the progression of obesity to comorbidities such as nonalcoholic steatohepatitis (NASH), type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) involve the gut-brain axis, a complex and highly coordinated system of peripheral appetite hormones and centrally mediated neuronal regulation. Data on the role of a gut-adipose axis in children with obesity-related comorbidities are sparse. We determined novel signals in the gut-adipose axis such as pro-uroguanylin (PUG) produced in the gut and spexin, predominantly produced in white adipose tissue along with traditional appetite/satiety hormones in insulin-resistant children with (NASH) and simple obesity.

Method: A total of 29 children (age: 8-17 years) in three groups, normal weight (NW; n=11; BMI<85th%), obese (n=9; BMI>95th%) and biopsy-proven NASH (n=9; NAS-score>2) were studied. Spexin, PUG, leptin, total (T)- and high molecular weight (HMW)-adiponectin and insulin were measured.

Results: Spexin, PUG and both T and HMW adiponectins were lower in children with NASH compared to both children with simple obesity and their NW counterparts, while leptin and insulin were higher (p<0.05). Spexin/leptin ratio and concentration of PUG were significantly lower (p<0.05) in children with NASH vs. simple obesity, whereas leptin and insulin were higher (p<0.05).

Conclusions: Lower concentrations of novel signals such as PUG and spexin in the current study suggest that perturbations in the gut-brain axis occur at an early age in the clinical course of obesity and NASH. The potential role of these novel gut-adipose axis signals, by themselves or in unison with other factors, in diagnosing and/or monitoring the development and/or progression of obesity-related comorbidities such as NASH, T2DM and CVD as well as the potential development of more directed therapies appears to be promising and warrants further studies.

Disclosure

M.D. Di Guglielmo: None. S. Mansoor: None. V. Uppal: None. K.N. Furuya: None. S. Kumar: None. P. Balagopal: None.

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