Insights into the Roles of Gut Microbes in Obesity
Figure 2
Schematic diagram of
signaling pathways triggered by bacterial components, saturated fatty
acids, and adipokines in epithelial and innate immune cells leading to
either activation or negative regulation of proinflammatory pathways related to
obesity and insulin resistance. (1) Lipopolysaccharide (LPS) from Gram-negative
bacteria and saturated fatty acids (SFAs) is recognized by toll-like receptor
(TLR) 4 activating proinflammatory pathways involving the MyD88 (myeloid
differentiation primary-response protein 88)-dependent and -independent
pathways that may lead to activation of nuclear factor (NF)-B and activator protein-1 (AP-1) with production
of pro-inflammatory cytokines. (2) Peptidoglycan (PGL) and lipoteichoic acid
from Gram-positive bacteria are recognized by TLR-2 triggering the activation of
the MyD88-dependent pathway. (3) Commensal bacteria and some probiotics may
suppress activation of NF-B cascade by (i) promotion of nuclear export of
NF-B subunit relA in complex with PPAR-; (ii) inhibition of IB ubiquitination and degradation, (iii)
induction of anti-inflammatory (IL10) cytokine production. (4) Leptin interacts
with its receptors (OBR) activating the signal transducer and activator of
transcription (STAT), and induces production of CCL2, proinflammatory
cytokines, and reactive oxygen species (ROS) causing endoplasmic reticulum (ER)
stress.
