Obesity-related glomerulopathy: recent advances in inflammatory mechanisms and related treatments

Abstract

Obesity-related glomerulopathy (ORG), which is an obesity-triggered kidney damage, has become a significant threat to human health. Several studies have recently highlighted the critical role of inflammation in ORG development. Additionally, excess adipose tissue and adipocytes in patients with obesity produce various inflammatory factors that cause systemic low-grade inflammation with consequent damage to vascular endothelial cells, exacerbating glomerular injury. Therefore, we conducted a comprehensive review of ORG and addressed the critical role of obesity-induced chronic inflammation in ORG pathogenesis and progression, which leads to tubular damage and proteinuria, ultimately impairing renal function. The relationship between obesity and ORG is facilitated by a network of various inflammation-associated cells (including macrophages, lymphocytes, and mast cells) and a series of inflammatory mediators (such as tumor necrosis factor-alpha, interleukin-6, leptin, adiponectin, resistin, chemokines, adhesion molecules, and plasminogen activator inhibitor-1) and their inflammatory pathways. Furthermore, we discuss a recently discovered relationship between micronutrients and ORG inflammation and the important role of micronutrients in the body's anti-inflammatory response. Therefore, assessing these inflammatory molecules and pathways will provide a strong theoretical basis for developing therapeutic strategies based on anti-inflammatory effects to prevent or delay the onset of kidney injury.

Differential Modulation of Catecholamine and Adipokine Secretion by the Short Chain Fatty Acid Receptor FFAR3 and α2-Adrenergic Receptors in PC12 Cells

“…Finally, we also show, for the first time to our knowledge, that FFAR3 activated by SCFAs directly stimulates the production and secretion of certain important adipokines, specifically of leptin and adiponectin, in PC12 cells, while the ketone BHB is capable of fully suppressing this effect, as well. Adipokines are cytokines produced and secreted by adipocytes, and several of them, particularly leptin and adiponectin, are involved in the modulation of obesity-associated inflammation, but also in neuroinflammation, cardiovascular inflammation, atherosclerosis, and inflammation of other tissues and organs [24][25][26][27]. Interestingly, leptin, in particular, is associated with increased SNS activity in humans (as part of its anorexigenic/food intake-reducing effect) [38], and, specifically in chromaffin cells, has been reported to modulate CA secretion.…”

“…Finally, we tested whether BHB, acting as an FFAR3 antagonist, can also inhibit SCFAinduced adipokine secretion from PC12 cells. Adipokines, such as leptin and adiponectin, are crucial for adipocyte differentiation (adipogenesis), but are also known to be involved in the inflammation of adipose and various other tissue types [24][25][26][27]. SCFAs, specifically butyrate, have been reported to promote adiponectin synthesis and secretion from pre-adipocytes via FFAR3 [22], an effect that mediates butyrate/FFAR3-dependent adipogenesis [22].…”