A Novel Pathway to the Manifestations of Metabolic Syndrome

Abstract

SONNENBERG, GABRIELE E., GLENN R. KRAKOWER, AND AHMED H. KISSEBAH. A novel pathway to the manifestations of metabolic syndrome. Obes Res. 2004;12:180 -186. Pathways leading from obesity to the manifestations of metabolic syndrome involve a number of metabolic risk factors, as well as adipokines, mediators of inflammatory response, thrombogenic and thrombolytic parameters, and vascular endothelial reactivity. Increased adipose tissue mass contributes to augmented secretion of proinflammatory adipokines, particularly tumor necrosis factor-␣ (TNF␣), along with diminished secretion of the "protective" adiponectin. In our view, TNF␣ and adiponectin are antagonistic in stimulating nuclear transcription factor-B (NF-B) activation. Through this activation, TNF␣ induces oxidative stress, which exacerbates pathological processes leading to oxidized low-density lipoprotein and dyslipidemia, glucose intolerance, insulin resistance, hypertension, endothelial dysfunction, and atherogenesis. NF-B activation further stimulates the formation of additional inflammatory cytokines, along with adhesion molecules which promote endothelial dysfunction. Elevated free fatty acid, glucose, and insulin levels enhance this NF-B activation and further downstream modulate specific clinical manifestations of metabolic syndrome.

Ghrelin in Type 2 diabetes mellitus and metabolic syndrome

“…Pathways leading from obesity to the manifestations of MS involve a number of metabolic risk factors (Sonnenberg et al, 2004). The resistance to insulin-stimulated glucose uptake is associated with multiple metabolic abnormalities.…”

Early treatment-related changes in diabetes and cardiovascular disease risk markers in first episode psychosis subjects

“…These proinflammatory agents are thought to induce oxidative stress thereby exacerbating underlying pathological processes leading to dyslipidemia, glucose intolerance, insulin resistance, and endothelial dysfunction that are common in obesity and type II diabetes mellitus (T2DM) (Sonnenberg et al, 2004). Previous cross-sectional studies found both higher (Togo et al, 2004) and lower (Richards et al, 2006) adiponectin levels in patients treated with olanzapine compared to healthy controls as well as lower levels in untreated patients compared to controls (Cohn et al, 2006).…”

Metabolic syndrome and risk of subsequent colorectal cancer

“…Also IL-6 concentrations reflected disease status and were commonly associated with metastatic disease [53] . TNF-α activates NF-κB (by phosphorylation of its inhibitor IκB), which increases production of NO, a substrate for reactive oxygen species (ROS) formation, and stimulates other inflammatory cytokines [54] . With respect to cancer, ROS can damage DNA by several processes including DNA base modification, deletions, frame shifts, strand breaks, DNA-protein cross-links, and chromosomal rearrangements.…”