Lipotoxicity in Kidney, Heart, and Skeletal Muscle Dysfunction

Abstract

Dyslipidemia is a common nutritional and metabolic disorder in patients with chronic kidney disease. Accumulating evidence supports the hypothesis that prolonged metabolic imbalance of lipids leads to ectopic fat distribution in the peripheral organs (lipotoxicity), including the kidney, heart, and skeletal muscle, which accelerates peripheral inflammation and afflictions. Thus, lipotoxicity may partly explain progression of renal dysfunction and even extrarenal complications, including renal anemia, heart failure, and sarcopenia. Additionally, endoplasmic reticulum stress activated by the unfolded protein response pathway plays a pivotal role in lipotoxicity by modulating the expression of key enzymes in lipid synthesis and oxidation. Here, we review the molecular mechanisms underlying lipid deposition and resultant tissue damage in the kidney, heart, and skeletal muscle, with the goal of illuminating the nutritional aspects of these pathologies.

Cardiac protection of functional chicken‐liver hydrolysates on the high‐fat diet induced cardio‐renal damages via sustaining autophagy homeostasis

“…It was reported that a long-term high-fat / sucrose diet promoted lipid deposition, glomerular hypertrophy, and apoptosis in the kidney. 3,41 In this study, a similar HFD induced pathological outcomes, including lipid deposition and hypertrophy in the renal glomerulus areas, as well as fibrosis in the renal cortex and outer medulla ( Fig. 2(b) and (d)).…”

“…Cardiovascular disease was also strongly associated with renal function because the kidney might directly influence the total blood volume and blood pressure. It was reported that a long‐term high‐fat / sucrose diet promoted lipid deposition, glomerular hypertrophy, and apoptosis in the kidney . In this study, a similar HFD induced pathological outcomes, including lipid deposition and hypertrophy in the renal glomerulus areas, as well as fibrosis in the renal cortex and outer medulla (Fig.…”

“…A high‐fat diet (HFD)‐fed rodent model has been widely used to imitate long‐term exposure to the risk factors associated with metabolic syndrome. The disturbance of lipid homeostasis leads to a cardiac lesion, which is often associated with human renal dysfunction . Recently, the term cardio‐renal syndrome (CRS) has been used to indicate different clinical conditions of the heart together with kidney dysfunction.…”

“…The disturbance of lipid homeostasis leads to a cardiac lesion, which is often associated with human renal dysfunction. 2,3 Recently, the term cardio-renal syndrome (CRS) has been used to indicate different clinical conditions of the heart together with kidney dysfunction. Metabolic CRS induced by an HFD is known as secondary CRS (also known as type 5 CRS), which is affected by systemic problems such as diabetes mellitus and insulin resistance.…”

Lipotoxicity and Diabetic Nephropathy: Novel Mechanistic Insights and Therapeutic Opportunities

“…Adipocytes act as fuel tanks for the storage of lipids and triglycerides. However, in non-adipocytes, which have a limited capacity to metabolize excessive lipids, their accumulation (steatosis) alter homeostasis and promote cell dysfunction [4].…”