Figure 2. An integrative and neuronal-dependent intestinal immunologic and metabolic network.

We propose that the intestine senses a change in the level of nutrients, cytokines, and microbiota-derived SCFAs, which triggers a gut/brain CCK- and GLP-1–dependent axis to regulate systemic inflammatory and glucose homeostasis. We further postulate that this proposed integrative and neuronal-dependent network is altered in obesity and diabetes and is targeted by metformin and bariatric surgical therapies to restore systemic metabolic homeostasis. In parallel, an influx of intestinal nutrients, bacterial products, and cytokines into the blood circulation induces inflammation and insulin resistance in the VAT and the liver and disrupts glucose homeostasis in obesity and diabetes.