116 7 Prospective
resistance or type II diabetes. Chronic inflammation is most likely derived from an
interaction of HFD with gut dysbiosis, leading to the overgrowth of G− bacteria
and the leakage of bacterial LPS. Upon activation of proinflammatory cytokines,
LPS can upregulate the expression of iNOS and HO-1, which directly lead to the
overproduction of NO and CO. Both gas molecules can competitively bind to
hemoglobin and myoglobin with O 2 , leading to metabolic hypoxia. The hypoxic
condition can subsequently induce HIF-1α, VEGF, and EPO, thereby driving angi-
ogenesis and adipogenesis. The commonly occurred hyperinsulinemia/hyperlepti
nemia in obesity might be explained by the ONOO−-mediated nitrosylation/nitra-
tion of insulin/leptin receptors. For BAT whitening to WAT in obesity, it might be
explained by the dramatic decline of NO that is derived from eNOS/nNOS and the
suppression of mitochondrial biogenesis.
By comparison of the gut microbiota between the healthy adults and the
patients with type II diabets, Qin et al. ( 2012 ) found the hypoproliferation of
butyrate-producing bacteria and the overgrowth of sulfate-reducing bacteria
among other abnormalities of gut microbiota. The butyrate-producing bacteria
are fiber-digested bacteria, whereas the sulfate-reducing bacteria are meat-
addicted bacteria. For example, the δ-proteobacteria, Desulfovibrio piger, with-
out any forms of sulfatases can only survive in the gut depending on the sulfate
released from Bacteroides thetaiotaomicron. It was found that chondroitin
Fig. 7.2 A hypothesized mechanism of adipogenesis/obesity. ARG l-arginine; BAT brown adi-
pose tissues; BMI body mass index; CO carbon monoxide; eNOS endothelial nitric oxide syn-
thase; EPO erythropoietin; G− Gram negative bacteria; G+ Gram positive bacteria; HIF-1α
hypoxia inducible factor α; HO- 1 heme oxygenase 1; iNOS inducible nitric oxide synthase; IR
insulin receptor; LFD low-fat diets; LPS lipopolysaccharide; nNOS neuronal nitric oxide syn-
thase; NO nitric oxide; SAT subcutaneous adipose tissues; SCFA short-chain fatty acids; VEGF
vascular endothelial growth factor; VAT visceral adipose tissues; WAT white adipose tissues