Acute Inflammation Is a Predisposing Factor for Weight Gain and Insulin Resistance

Abstract

In the course of infection and intense endotoxemia processes, induction of a catabolic state leading to weight loss is observed in mice and humans. However, the late effects of acute inflammation on energy homeostasis, regulation of body weight and glucose metabolism are yet to be elucidated. Here, we addressed whether serial intense endotoxemia, characterized by an acute phase response and weight loss, could be an aggravating or predisposing factor to weight gain and associated metabolic complications. Male Swiss Webster mice were submitted to 8 consecutive doses of lipopolysaccharide (10 mg/kg LPS), followed by 10 weeks on a high-fat diet (HFD). LPS-treated mice did not show changes in weight when fed standard chow. However, when challenged by a high-fat diet, LPS-treated mice showed greater weight gain, with larger fat depot areas, increased serum leptin and insulin levels and impaired insulin sensitivity when compared to mice on HFD only. Acute endotoxemia caused a long-lasting increase in mRNA expression of inflammatory markers such as TLR-4, CD14 and serum amyloid A (SAA) in the adipose tissue, which may represent the key factors connecting inflammation to increased susceptibility to weight gain and impaired glucose homeostasis. In an independent experimental model, and using publicly available microarray data from adipose tissue from mice infected with Gram-negative bacteria, we performed gene set enrichment analysis and confirmed upregulation of a set of genes responsible for cell proliferation and inflammation, including TLR-4 and SAA. Together, we showed that conditions leading to intense and recurring endotoxemia, 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.

Adipokines, Hepatokines and Myokines: Focus on Their Role and Molecular Mechanisms in Adipose Tissue Inflammation

“…The SAA4 isoform is constitutively expressed at relatively low levels in both the human and mouse liver, although its function is unknown. Unlike SAA4, the expression of SAA1, SAA2, and SAA3 is highly induced in the AT and liver after inflammatory stimuli such as LPS treatment ( 163 , 164 ).…”

Ovol1/2 loss‐induced epidermal defects elicit skin immune activation and alter global metabolism

“…Barrier defects are associated with inflammatory skin diseases such as psoriasis and atopic dermatitis (Proksch et al , 2006; Elias & Wakefield, 2014; Dainichi et al , 2018). Moreover, tantalizing links exist between skin inflammation and whole‐body perturbation, evident through higher incidence of psoriasis and atopic dermatitis in patients with obesity (Zheng, 2014; Brunner et al , 2017), growth failure in patients with ichthyosis the clinical severity of which parallels the extent of barrier dysfunction (Dereksson et al , 2012; Elias et al , 2012; Yamamoto et al , 2020), and weight loss in animals following acute inflammation (Gabay & Kushner, 1999; de Oliveira et al , 2022). However, little is known about how epidermal/barrier dysregulation shapes the skin immune microenvironment in the absence of any blatant disease‐inducing stimuli, and how skin defects instigate whole‐body physiological and metabolic changes.…”

A Metabolite Perspective on the Involvement of the Gut Microbiota in Type 2 Diabetes

“…In a subsequent investigation, it was discovered that T2D patients had higher postprandial LPS levels than typical healthy participants [75]. Campa et al conducted a study on acutely inflamed mice treated with a HFD and LPS; the researchers observed that these mice exhibited several adverse effects, including increased body weight, impaired insulin sensitivity, acute endotoxemia, upregulated expression of the inflammatory marker TLR-4, and impaired glucose homeostasis [76]. These findings indicate that diabetes causes an increase in intestinal permeability, allowing bacteria and LPS to easily enter the bloodstream.…”