Low-Grade Inflammation, Obesity, and Diabetes

Abstract

Obesity and its comorbidities are closely related to the inflammatory environment created by expanded adipose tissue. Several mechanisms trigger inflammation in adipose tissue, including excess fatty acids, hypoxia, and activation of the inflammasome. Inflammation is characterized by the abundance of immune cells, particularly M1 macrophages and T lymphocytes, which have increased secretion of proinflammatory cytokines that act to perpetuate systemic inflammation and induce insulin resistance. The gut microbiota is also involved in obesity-induced inflammation via LPS-related endotoxemia that induces cytokine secretion and insulin resistance. Innate lymphoid type 2 cells, regulatory T cells, and interleukine (IL)-10 counteract the inflammation and insulin resistance, establishing classical or metabolically healthy obesity.

Endoplasmic reticulum stress and the unfolded protein response in pancreatic islet inflammation

“…Obesity, a major risk factor for T2D, is characterized by systemic low-grade chronic inflammation in the form of increased circulating levels of pro-inflammatory cytokines such as TNF, IL1β, and IL6 and lower levels of anti-inflammatory adipokines such as adiponectin and omentin (Pereira & Alvarez-Leite 2014). In line with this, elevated circulating levels of pro-inflammatory cytokines characterize the early (or pre-clinical) stages of T2D and exhibit a graded increase with the disease progression (Duncan et al 2003, Grossmann et al 2015.…”

Influence of obesity on serum uric acid level in postmenopausal women

“…0,335** hsCRP (mg/L) 0,234* * -p<0,05, ** -p<0,001; TM -telesna masa; ITM -indeks telesne mase; HOMA-IR -surogat marker insulinske rezistencije; HDL-holesterol -koncentracija holesterola u lipoproteinima velike gustine; LDLholesterol -koncentracija holesterola u lipoproteinima male gustine; SKP -sistolni krvni pritisak; DKPdijastolni krvni pritisak; RBP4-retinol -vezujući protein 4; hsCRP -visokosenzitivni C-reaktivni protein. Objašnjenje za ovakav nalaz može biti u disfunkciji visceralnog masnog tkiva kod gojaznih, koji je medijator u nastanku i razvoju brojnih komorbiditeta -insulinske rezistencije, dijabetesa tip 2 i hipertenzije [7,8]. Stanje hronične inflamacije niskog stepena, usko povezano sa visceralnom gojaznošću, može uticati na signalne puteve insulina putem supresije insulinskih receptora preko serinske fosforilacije supstrata insulinskih receptora [12].…”

“…www.tmg.org.rs UVOD Mokraćna kiselina (MK) je slaba organska kiselina (pH 5,8), koja pri fiziološkoj vrednosti pH krvotokom cirkuliše u jonizovanom obliku, kao mononatrijum-urat [1]. Ona predstavlja konačni razgradni produkt purinskih baza, adenina i guanina, koje čine sastavni deo DNK i RNK [1].…”

“…Zbog toga je kod gojaznih osoba poremećena ravnoteža između ovih molekula, tako da povećani broj adipocita i makrofaga produkuje više proinflamatornih adipocitokina (leptin, retinol-vezujući protein 4 [RBP4], faktor nekroze tumora alfa [TNF-α], interleukina 6 [IL-6]) i manje antiinflamatornih peptida (adiponektin), dovodeći do stanja koje podstiče razvoj insulinske rezistencije i endotelne disfunkcije [7,8].…”

Metabolically Healthy Obesity

“…In fact, administration of antibacterial agents targeting caecal aerobic and anaerobic bacteria with high efficiency (namely norfloxacin and ampicillin) to mice fed a high-fat diet and ob/ob mice significantly enhanced their global glucose tolerance, decreased their fasting glycaemia and circulating LPS levels, and improved the secretion of Adiponectin [66], known for its positive effects on insulin sensitivity [43]. The current model of obesity-associated endotoxemia posits that gut-derived LPS and free fatty acids activate M1 macrophages which, together with other immune cells, create a hepatic and physiologic inflammatory process sustaining the above-mentioned obesity-related comorbidities [67].…”