Obesity, Inflammation, and Insulin Resistance

Obesity is related to a low-grade inflammation, and increased production and secretion of inflammatory factors including TNF-α and IL-6 modulate insulin sensitivity by altering key steps in the insulin signaling pathway, which is responsible for subsequent insulin resistance.

“Meanwhile, obesity is related to a low-grade inflammation, the increased production and secretion of multifarious inflammatory factors including TNF-α, IL-6 modulate insulin sensitivity by altering some key steps in the insulin signaling pathway, which is responsible for the subsequent insulin resistance (34–36).”

Adipocytes are the unique source of secreted adipokines such as leptin and adiponectin, which can promote insulin sensitivity, and resistin and retinol-binding protein 4, which can impair insulin sensitivity.

“Adipocytes are the unique source of secreted adipokines such as leptin and adiponectin, which can promote insulin sensitivity, as well as resistin and retinol-binding protein 4 (RBP4), which can impair insulin sensitivity (83)(84)(85).”

Elevated levels of TNF-α, IL-6, and C-reactive protein have been shown in individuals with insulin resistance and diabetes.

“Consistent with this, elevated levels of the proinflammatory cytokines TNF-α, IL-6, and C-reactive protein (CRP) have been shown in individuals with insulin resistance and diabetes (for review, see refs.[83][84][85].”

Several cytokines and chemokines, including CCL2, IL-6, IL-1β, MIF, and TNF-α, can be released by adipocytes and macrophages.

“Several cytokines and chemokines, such as CCL2, IL-6, IL-1β, macrophage migration inhibitory factor (MIF), and TNF-α, can be released by adipocytes and macrophages (83)(84)(85).”

Inflammation lies at the heart of many of these processes, and pathways involving NF-κB are especially core.

“inflammation lies at the heart of many of these processes, and pathways involving NF-κB (see e.g. http://www.nf-kb.org/) are especially core here”

Obese adipocytes and infiltrated immune cells secrete a large amount of inflammatory mediators that promote a proinflammatory state through activation of IKKβ-NF-Kβ and JNK-Ap1 signaling pathways.

“Obese adipocytes and infiltrated immune cells secrete a large amount of inflammatory mediators that promote a proinflammatory state through the activation of IKKβ-NF-Kβ and the JNK-Ap1 signaling pathways ([151](#B151)).”