Role of microbiota-derived lipopolysaccharide in adipose tissue inflammation, adipocyte size and pyroptosis during obesity

Abstract

It has been established that ingestion of a high-fat diet increases the blood levels of lipopolysaccharides (LPS) from Gram-negative bacteria in the gut. Obesity is characterised by low-grade systemic and adipose tissue inflammation. This is suggested to be implicated in the metabolic syndrome and obesity. In the present review, we hypothesise that LPS directly and indirectly participates in the inflammatory reaction in adipose tissue during obesity. The experimental evidence shows that LPS is involved in the transition of macrophages from the M2 to the M1 phenotype. In addition, LPS inside adipocytes may activate caspase-4/5/11. This may induce a highly inflammatory type of programmed cell death (i.e. pyroptosis), which also occurs after infection with intracellular pathogens. Lipoproteins with or without LPS are taken up by adipocytes. Large adipocytes are more metabolically active and potentially more exposed to LPS than small adipocytes are. Thus, LPS might be involved in defining the adipocyte death size and the formation of crown-like structures. The adipocyte death size is reached when the intracellular concentration of LPS initiates pyroptosis. The mechanistic details remain to be elucidated, but the observations indicate that adipocytes are stimulated to cell death by processes that involve LPS from the gut microbiota. There is a complex interplay between the composition of the diet and microbiota. This influences the amount of LPS that is translocated from the gut. In particular, the lipid content of a meal may correlate with the amount of LPS built in to chylomicrons.

Keywords: ASC apoptosis-associated speck-like protein containing a CARD; AT adipose tissue; CARD caspase activation and recruitment domain; CD cluster of differentiation; CM chylomicron; GSIS glucose-stimulated insulin secretion; HFD high-fat diet; LBP lipopolysaccharide-binding protein; LPS lipopolysaccharide; M1 macrophage phenotype 1; M2 macrophage phenotype 2; NLR nucleotide-binding oligomerisation domain (NOD)-like receptor; NLRP3 NOD-like receptor family pyrin domain containing-3; NOD nucleotide-binding oligomerisation domain; SAT subcutaneous adipose tissue; TLR toll-like receptor; TLR4 toll-like receptor 4; VAT visceral adipose tissue; sCD14 soluble cluster of differentiation 14; Adipocyte death size; Adipose tissue inflammation; Gut microbiota; Lipopolysaccharide; Pyroptosis.