Obesity, kidney dysfunction, and inflammation: interactions in hypertension

Abstract

Obesity contributes 65-75% of the risk for human primary (essential) hypertension which is a major driver of cardiovascular and kidney diseases. Kidney dysfunction, associated with increased renal sodium reabsorption and compensatory glomerular hyperfiltration, plays a key role in initiating obesity-hypertension and target organ injury. Mediators of kidney dysfunction and increased blood pressure include 1) elevated renal sympathetic nerve activity (RSNA); 2) increased antinatriuretic hormones such as angiotensin II and aldosterone; 3) relative deficiency of natriuretic hormones; 4) renal compression by fat in and around the kidneys; 5) activation of innate and adaptive immune cells that invade tissues throughout the body, producing inflammatory cytokines/chemokines that contribute to vascular and target organ injury, and exacerbate hypertension. These neurohormonal, renal, and inflammatory mechanisms of obesity-hypertension are interdependent. For example, excess adiposity increases the adipocyte-derived cytokine leptin which increases RSNA by stimulating the central nervous system proopiomelanocortin-melanocortin 4 receptor pathway. Excess visceral, perirenal and renal sinus fat compress the kidneys which, along with increased RSNA, contribute to renin-angiotensin-aldosterone system activation, although obesity may also activate mineralocorticoid receptors independent of aldosterone. Prolonged obesity, hypertension, metabolic abnormalities, and inflammation cause progressive renal injury, making hypertension more resistant to therapy and often requiring multiple antihypertensive drugs and concurrent treatment of dyslipidemia, insulin resistance, diabetes, and inflammation. More effective anti-obesity drugs are needed to prevent the cascade of cardiorenal, metabolic, and immune disorders that threaten to overwhelm health care systems as obesity prevalence continues to increase.

Microbiome First Medicine in Health and Safety

“…Obesity is one of the major conditions that gives rise to a myriad of comorbid, inflammation driven, chronic diseases particularly as aging progresses [ 62 , 63 ]. Table 2 illustrates examples of 43 comorbid NCDs for obesity [ 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 ]. The obese population carries one of the highest risks for multiple future NCDs of any disease-burdened cohort.…”

Sex differences in the impact of parental obesity on offspring cardiac SIRT3 expression, mitochondrial efficiency, and diastolic function early in life

“…Our findings suggest that parental obesity programs their offspring not only for obesity and associated metabolic disorders but also for cardiac dysfunction, at least in male offspring. The longer that obesity and metabolic disorders are sustained, the greater the risk of developing cardiovascular and metabolic diseases (36).…”

Perirenal Adipose Tissue Inflammation: Novel Insights Linking Metabolic Dysfunction to Renal Diseases

“…Given the intimate relation between PRAT and the kidney, either due to their spatial proximity or due to their common innervation and vascularization, PRAT expansion, dysfunction, and inflammation are thought to have a pronounced impact on renal function ( 149 , 150 ). PRAT thickness is increased in patients with MetS, which is accompanied by increases in oxidative stress and renal microvascular proliferation ( 151 ).…”