From fat to filter: the effect of adipose tissue-derived signals on kidney function

Abstract

Obesity is associated with severe consequences for the renal system, including chronic kidney disease, kidney failure and increased mortality. Obesity has both direct and indirect effects on kidney health through several mechanisms, including activation of the renin–angiotensin system, mechanical compression, inflammation, fibrosis, increased filtration barrier permeability and renal nerve activity. The expansion of adipose tissue through hypertrophy and hyperplasia can induce haemodynamic changes that promote glomerular hyperfiltration to compensate for the greater metabolic demands of the increased body weight. Adipose expansion is also associated with the release of adipokines and pro-inflammatory cytokines, hyperinsulinaemia and insulin resistance, which exert direct and indirect effects on kidney function via various mechanisms. Increased uptake of fatty acids by the kidney leads to alterations in lipid metabolism and lipotoxicity, also contributing to the pro-inflammatory and pro-fibrotic environment. The role of the adipose tissue–brain–kidney axis in the obesity-associated decline in renal function is sustained by studies showing that stimulation of adipose tissue sensory neurons by locally released factors increases renal sympathetic nerve activity. Conversely, pre-existent kidney disease can contribute to adipose dysfunction through the accumulation of uraemic toxins and hormonal changes. These findings highlight the importance of crosstalk between adipose tissue and the kidneys and provide insights into the mechanisms underlying the associations between obesity and kidney disease.