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bioRxiv · 10.1101/583773

Acute inflammation is a predisposing factor for weight gain and insulinresistance

Oliveira, E. M.·Silva, J. C.·Ascar, T. P.·Sandri, S.·Marchi, A.·Migliorini, S.·Nakaya, H. T. I.·Fock, R.·Campa, A.
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Abstract

AimIntense endotoxaemia and infection are able to reduce appetite and induce a catabolic state, therefore leading to weight loss. However, it is underexplored its late effects on energy homeostasis, regulation of body weight and glucose metabolism. Here we addressed whether serial intense endotoxaemia, characterized by an acute phase response and weight loss, could be an aggravating or predisposing factor to diet-induced obesity (DIO) and associated metabolic impairments.\n\nMethodsMale Swiss Webster mice were submitted to 8 consecutive doses of lipopolysaccharide (LPS - 10 mg/kg), followed by 10 weeks in high-fat diet (HFD).\n\nResultsAfter the end of the acute endotoxaemia period, mice under chow diet recovered their weight rapidly, within one-week recovery period, which remained similar to its control counterparts. However, acute endotoxaemia caused a long-lasting adipose tissue expression of the inflammatory markers TLR-4, CD14 and serum amyloid A (SAA) and, when challenged by a HFD, LPS-treated mice gained more weight, showed increased fat depots, leptin and insulin levels, and also impaired insulin sensitivity.\n\nConclusionsLPS-treated mice showed a higher susceptibility to the harmful effects of a subsequent HFD. Conditions leading to intense and recurrent endotoxaemia, such as common childhood bacterial infections, may resound for a long time and aggravate the effects of a western diet. If confirmed in humans, infections should be considered an additional factor contributing to obesity and type 2 diabetes epidemics and additionally impose more rigorous dietary recommendations for patients in post-infection recovery.\n\nBullet pointsO_LIIntense endotoxemia causes a long-lasting increase in the expression of inflammatory markers in adipose tissue.\nC_LIO_LIIntense endotoxemia is a predisposing factor to diet-induced obesity and insulin resistance.\nC_LIO_LIInfections may contribute to weight gain when associated to a western diet.\nC_LI

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Oliveira, E. M., Silva, J. C., Ascar, T. P., Sandri, S., Marchi, A., Migliorini, S., Nakaya, H. T. I., Fock, R., Campa, A.. 2019-03-25. Acute inflammation is a predisposing factor for weight gain and insulinresistance. https://doi.org/10.1101/583773

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