Resistance to insulin metabolic signaling in adipose tissue contributes to the lipid abnormalities in obese, hyperinsulinemic, insulin-resistant patients who develop the cardiorenal syndrome. These same metabolic dyslipidemic abnormalities can be found in conditions of caloric energy restriction with decreased adiposity or normal insulin levels, such as anorexia, starvation or non-diabetic kidney disease. In this review, we assess hypoglycemia as an alternative physiological explanation for the biochemical and lipid findings in conditions of insulin resistance (IR). Therefore, PubMed databases (1961–2010) were searched for articles on the effect of hypoglycemia and starvation on non-esterified fatty acid (NEFA) elevation and abnormalities in insulin signaling in muscles as well as abnormal kidney metabolism. The search included articles on NEFA and their role in triglyceride (TG) and high-density lipoprotein (HDL) metabolism, as well as kidney and heart disease. Available studies support that hypoglycemia increases NEFA generation from adipose tissue. Elevated levels of NEFA induce increased plasma levels of TG and decreased levels of HDL cholesterol, and may cause direct kidney and myocardial damage. IR of adipose and skeletal muscle tissue, and the elevation in insulin levels in obese, insulin-resistant patients could be explained by an adaptation to their carbohydrate intake. These molecular abnormalities in insulin metabolic signaling can also be found in hypoglycemia or starvation. In conclusion, IR of adipose tissue cannot fully explain the lipid abnormalities observed in the cardiorenal syndrome. Decreased blood glucose levels (e.g. hypoglycemia) occur frequently in patients at risk for this syndrome. Hypoglycemia-induced increases in NEFA levels can promote lipid abnormalities that contribute to IR and the cardiorenal syndrome.

Keywords:
Non-esterified fatty acids, Obesity, Cardiorenal syndrome, Dyslipidemia, Hypoglycemia, Insulin resistance
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