Oleic acid and peanut oil high in oleic acid reverse the inhibitory effect of insulin production of the inflammatory cytokine TNF-alpha both in vitro and in vivo systems.
BACKGROUND
Chronic inflammation is a key player in pathogenesis. The inflammatory cytokine, tumor necrosis factor-alpha is a well known inflammatory protein, and has been a therapeutic target for the treatment of diseases such as Rheumatoid Arthritis and Crohn's Disease. Obesity is a well known risk factor for developing non-insulin dependent diabetes melitus. Adipose tissue has been shown to produce tumor necrosis factor-alpha, which has the ability to reduce insulin secretion and induce insulin resistance. Based on these observations, we sought to investigate the impact of unsaturated fatty acids such as oleic acid in the presence of TNF-alpha in terms of insulin production, the molecular mechanisms involved and the in vivo effect of a diet high in oleic acid on a mouse model of type II diabetes, KKAy.


METHODS
The rat pancreatic beta cell line INS-1 was used as a cell biological model since it exhibits glucose dependent insulin secretion. Insulin production assessment was carried out using enzyme linked immunosorbent assay and cAMP quantification with competitive ELISA. Viability of TNF-alpha and oleic acid treated cells was evaluated using flow cytometry. PPAR-gamma translocation was assessed using a PPRE based ELISA system. In vivo studies were carried out on adult male KKAy mice and glucose levels were measured with a glucometer.


RESULTS
Oleic acid and peanut oil high in oleic acid were able to enhance insulin production in INS-1. TNF-alpha inhibited insulin production but pre-treatment with oleic acid reversed this inhibitory effect. The viability status of INS-1 cells treated with TNF-alpha and oleic acid was not affected. Translocation of the peroxisome proliferator- activated receptor transcription factor to the nucleus was elevated in oleic acid treated cells. Finally, type II diabetic mice that were administered a high oleic acid diet derived from peanut oil, had decreased glucose levels compared to animals administered a high fat diet with no oleic acid.


CONCLUSIONS
Oleic acid was found to be effective in reversing the inhibitory effect in insulin production of the inflammatory cytokine TNF-alpha. This finding is consistent with the reported therapeutic characteristics of other monounsaturated and polyunsaturated fatty acids. Furthermore, a diet high in oleic acid, which can be easily achieved through consumption of peanuts and olive oil, can have a beneficial effect in type II diabetes and ultimately reverse the negative effects of inflammatory cytokines observed in obesity and non insulin dependent diabetes mellitus.
Vassiliou
Evros K
EK
Department of Biological Sciences, Kean University, 1000 Morris Avenue, Union, New Jersey 07083, USA. evassili@kean.edu
Gonzalez
Andres
A
Garcia
Carlos
C
Tadros
James H
JH
Chakraborty
Goutam
G
Toney
Jeffrey H
JH
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001786:Blood Glucose / Q000187:drug effects; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood; D018836:Inflammation Mediators / Q000494:pharmacology*; D007328:Insulin / Q000096:biosynthesis*; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D019301:Oleic Acid / Q000008:administration & dosage / Q000032:analysis / Q000494:pharmacology*; D047495:PPAR gamma / Q000378:metabolism; D000074241:Peanut Oil; D010938:Plant Oils / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D021381:Protein Transport; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D001786:Blood Glucose; D018836:Inflammation Mediators; D007328:Insulin; D047495:PPAR gamma; D000074241:Peanut Oil; D010938:Plant Oils; D014409:Tumor Necrosis Factor-alpha; D019301:Oleic Acid; D000242:Cyclic AMP