Kidney Res Clin Pract.  2012 Sep;31(3):177-185.

Plasma leptin concentrations are greater in type II diabetic patients and stimulate monocyte chemotactic peptide-1 synthesis via the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway

• Cha JJ
• Hyun YY
• Jee YH
• Lee MJ
• Han KH
• Kang YS
• Han SY
• Cha DR

Abstract

BACKGROUND
Leptin is an adipokine that is recently reported to be a biomarker of systemic inflammation. Although atherosclerosis causes cardiovascular diseases, it is not clear whether leptin contributes to the acceleration of this process. In this study, we investigated whether alterations of plasma leptin levels were related to diabetic nephropathy and systemic inflammation. In addition, we examined the physiologic action of leptin in cultured vascular smooth muscle cells (VSMCs).
METHODS
A total of 126 type 2 diabetic participants and 37 healthy controls were studied. The diabetic participants were divided into three groups according to stage of nephropathy. We investigated whether leptin induced monocyte chemotactic peptide-1 (MCP-1) synthesis through the mitogen-activated protein kinase (MAPK) pathway using cultured VSMCs.
RESULTS
Plasma leptin concentrations were significantly higher in the diabetic group than in the controls. Plasma leptin levels were positively correlated with body mass index, fasting and postprandial blood glucose, hemoglobin A1c, total cholesterol, urinary albumin excretion, high-sensitivity C-reactive protein (hsCRP), and MCP-1 plasma levels, and negatively correlated with creatinine clearance values. In cultured VSMCs, leptin increased MCP-1 production in a dose-dependent manner, and this stimulating effect of leptin on MCP-1 expression was reversed by the MAPK (MEK) inhibitor PD98059. In addition, leptin stimulated the phosphorylation of MEK, extracellular signal-regulated kinase, and E26-like transcription factor, which are components of the MAPK pathway.
CONCLUSION
Overall, these findings suggest that activation of leptin synthesis may promote MCP-1 activation in a diabetic environment via the MAPK pathway in VSMCs and that it possibly contributes to the acceleration of atherosclerosis.

Keyword

Atherosclerosis; Diabetes mellitus; Leptin; Monocyte chemotactic peptide-1; Vascular smooth muscle cell

MeSH Terms

Acceleration
Adipokines
Atherosclerosis
Blood Glucose
Body Mass Index
C-Reactive Protein
Cardiovascular Diseases
Cholesterol
Creatinine
Diabetes Mellitus
Diabetic Nephropathies
Fasting
Flavonoids
Hemoglobins
Humans
Inflammation
Leptin
Monocytes
Muscle, Smooth, Vascular
Phosphorylation
Phosphotransferases
Plasma
Protein Kinases
Transcription Factors
Adipokines
Blood Glucose
C-Reactive Protein
Cholesterol
Creatinine
Flavonoids
Hemoglobins
Leptin
Phosphotransferases
Protein Kinases
Transcription Factors