Increased plasma concentration of macrophage Migration Inhibitory Factor (MIF) and MIF mRNA in mononuclear cells in the obese and the suppressive action of metformin

Paresh Dandona, Ahmad Aljada, Husam Ghanim, Priya Mohanty, Chandana Tripathy, Deborah Hofmeyer, Ajay Chaudhuri

Research output: Contribution to journalArticle

141 Citations (Scopus)

Abstract

The objective of the study was to determine whether plasma migration inhibitor factor (MIF) concentration and mononuclear cell (MNC) mRNA are elevated in obesity and whether treatment with metformin reduces plasma MIF concentration. Forty obese subjects [body mass index (BMI), 37.5 ± 4.9 kg/m2] and 40 nonobese healthy subjects (BMI, 22.6 ± 3.4 kg/ m2) had their plasma MIF, glucose, insulin, free fatty acids (FFAs) and C-reactive protein (CRP) concentrations measured. Sixteen obese patients and 16 nonobese healthy subjects had RNA prepared from MNCs. Eight obese subjects with normal glucose concentration were treated with metformin 1 g (Glucophage XR; 1000 mg twice daily) twice daily for 6 wk. Eight obese subjects were used as controls. Plasma concentration of glucose, insulin, FFAs, and MIF was measured by appropriate assays. mRNA for MIF was measured by real-time PCR. Forty obese subjects had a fasting concentration of MIF of 2.8 ± 2.0 ng/ml, whereas 40 nonobese subjects had a fasting MIF concentration of 1.2 ± 0.6 ng/ml (P < 0.001). Plasma MIF concentrations were significantly related to BMI (r = 0.52; P < 0.001). mRNA for MIF was correlated to plasma FFAs (r = 0.40; P < 0.05) and plasma CRP (r = 0.42; P < 0.05) concentrations. Eight obese subjects had their fasting blood samples taken before and after taking a slow-release preparation of metformin at 1,2,4, and 6 wk. The mean plasma concentration fell from 2.3 ± 1.4 to 1.6 ± 1.2 ng/ml at 6 wk (P < 0.05). Obese subjects not on treatment with metformin showed no change. During the period of treatment with metformin, the body weight did not change and the plasma concentration of glucose, insulin, and FFAs did not alter. We conclude that: 1) plasma MIF concentrations and MIF mRNA expression in the MNCs are elevated in the obese, consistent with a proinflammatory state in obesity; 2) these increases in MIF are related to BMI, FFA concentrations, and CRP; 3) metformin suppresses plasma MIF concentrations in the obese, suggestive of an antiinflammatory effect of this drug; and 4) this action of metformin may contribute to a potential antiatherogenic effect, which may have implications for the reduced cardiovascular mortality observed with metformin therapy in type 2 diabetes mellitus.

Original languageEnglish (US)
Pages (from-to)5043-5047
Number of pages5
JournalJournal of Clinical Endocrinology and Metabolism
Volume89
Issue number10
DOIs
StatePublished - Oct 2004
Externally publishedYes

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Macrophage Migration-Inhibitory Factors
Metformin
Plasmas
Messenger RNA
Nonesterified Fatty Acids
Body Mass Index
C-Reactive Protein
Glucose
Fasting
Insulin
Healthy Volunteers
Obesity
Body Weight Changes
Therapeutics
Medical problems
Type 2 Diabetes Mellitus
Blood Proteins
Real-Time Polymerase Chain Reaction
Anti-Inflammatory Agents
Assays

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Increased plasma concentration of macrophage Migration Inhibitory Factor (MIF) and MIF mRNA in mononuclear cells in the obese and the suppressive action of metformin. / Dandona, Paresh; Aljada, Ahmad; Ghanim, Husam; Mohanty, Priya; Tripathy, Chandana; Hofmeyer, Deborah; Chaudhuri, Ajay.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 89, No. 10, 10.2004, p. 5043-5047.

Research output: Contribution to journalArticle

Dandona, Paresh ; Aljada, Ahmad ; Ghanim, Husam ; Mohanty, Priya ; Tripathy, Chandana ; Hofmeyer, Deborah ; Chaudhuri, Ajay. / Increased plasma concentration of macrophage Migration Inhibitory Factor (MIF) and MIF mRNA in mononuclear cells in the obese and the suppressive action of metformin. In: Journal of Clinical Endocrinology and Metabolism. 2004 ; Vol. 89, No. 10. pp. 5043-5047.
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abstract = "The objective of the study was to determine whether plasma migration inhibitor factor (MIF) concentration and mononuclear cell (MNC) mRNA are elevated in obesity and whether treatment with metformin reduces plasma MIF concentration. Forty obese subjects [body mass index (BMI), 37.5 ± 4.9 kg/m2] and 40 nonobese healthy subjects (BMI, 22.6 ± 3.4 kg/ m2) had their plasma MIF, glucose, insulin, free fatty acids (FFAs) and C-reactive protein (CRP) concentrations measured. Sixteen obese patients and 16 nonobese healthy subjects had RNA prepared from MNCs. Eight obese subjects with normal glucose concentration were treated with metformin 1 g (Glucophage XR; 1000 mg twice daily) twice daily for 6 wk. Eight obese subjects were used as controls. Plasma concentration of glucose, insulin, FFAs, and MIF was measured by appropriate assays. mRNA for MIF was measured by real-time PCR. Forty obese subjects had a fasting concentration of MIF of 2.8 ± 2.0 ng/ml, whereas 40 nonobese subjects had a fasting MIF concentration of 1.2 ± 0.6 ng/ml (P < 0.001). Plasma MIF concentrations were significantly related to BMI (r = 0.52; P < 0.001). mRNA for MIF was correlated to plasma FFAs (r = 0.40; P < 0.05) and plasma CRP (r = 0.42; P < 0.05) concentrations. Eight obese subjects had their fasting blood samples taken before and after taking a slow-release preparation of metformin at 1,2,4, and 6 wk. The mean plasma concentration fell from 2.3 ± 1.4 to 1.6 ± 1.2 ng/ml at 6 wk (P < 0.05). Obese subjects not on treatment with metformin showed no change. During the period of treatment with metformin, the body weight did not change and the plasma concentration of glucose, insulin, and FFAs did not alter. We conclude that: 1) plasma MIF concentrations and MIF mRNA expression in the MNCs are elevated in the obese, consistent with a proinflammatory state in obesity; 2) these increases in MIF are related to BMI, FFA concentrations, and CRP; 3) metformin suppresses plasma MIF concentrations in the obese, suggestive of an antiinflammatory effect of this drug; and 4) this action of metformin may contribute to a potential antiatherogenic effect, which may have implications for the reduced cardiovascular mortality observed with metformin therapy in type 2 diabetes mellitus.",
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AU - Hofmeyer, Deborah

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