Academic journal article Iranian Journal of Public Health

Effect of Omega-3 Supplementation on Lipocalin 2 and Retinol-Binding Protein 4 in Type 2 Diabetic Patients

Academic journal article Iranian Journal of Public Health

Effect of Omega-3 Supplementation on Lipocalin 2 and Retinol-Binding Protein 4 in Type 2 Diabetic Patients

Article excerpt


Lipocalins family encompasses more than twenty different proteins. Theses mall, soluble protein shave different sequences with only 20% similarity to each other. However, all of them composed of8 antiparallel beta-barrels. Lipophilic substances such as free fatty acids, retinoids, arachidonic acid and steroids pass through a hole inside the barrel (1, 2). Lipocalin 2 is a 25kDa glycoprotein, identified as neutrophil gelatinase associated lipocalin (NGAL), neutrophil lipocalin (NL) and 24P3 oncogene. This protein secreted mainly from the liver and adipose tissue (3). LCN 2 expression is increased by substances that improve insulin resistance and is decreased by thiazolidinediones (TZD) (4). Lipocalin 2 up-regulates peroxisome proliferator-activated receptor gamma (PPARγ) and its target genes including leptin, adiponectin, fatty acid synthase (FAS) and lipoprotein lipase in adipose tissue (5).

Retinol-binding protein 4 (RBP 4) belongs to lipocalins family and transfers small hydrophobic molecules form membranes (6). Its gene locates on the long arm of chromosome 10, near glucose homeostasis area in European-Caucasian ethnicity and near region of type 2 diabetes in Mexicans-Africans (7, 8). The protein consists of 201 amino acids and its molecular weight is 21kDa (9, 10). The highest expression is seen in the liver and adipose tissue. RBP 4 increased in the early stages of stroke and cardiovascular disease (11-13). Serum RBP 4 might have a negative correlation with insulin resistance and development of T2DM (14, 15). RBP 4 is connected to diabetes through insulin secretion, and pancreas beta cells play a key role in this relationship (15). Significant weight loss by diet, lifestyle modifications and bariatric surgery may reduce RBP 4 levels (16). Improvement in insulin resistance by exercising also reduces RBP 4 concentration (17). RBP4 concentrations increase in humans with obesity and type 2 diabetes. Rosiglitazone, an insulin-sensitizing drug that activates PPARγ, decreases RBP4 concentrations. Lowering RBP 4 might be a novel strategy that helps type 2 diabetic patients (18).

Ecological studies have shown that marine foods may negatively associate with insulin resistance in obese subjects. Meta-analysis reports omega-3 fatty acids in the Asian population, unlike the western population, protect against T2DM. However, Asian patients have lower levels of omega-3 than western patients in their plasma and cell membranes (19). EPA correlates with up-regulation of PPARγ and down-regulation of interleukin-6 and tumor necrosis factor-alpha (TNFα). Results suggest that EPA probably change PPARγ activation and expression (20).

We carried out this study to compare the effect of omega-3 supplementation versus placebo on LCN 2 and RBP 4 levels in type 2 diabetic patients. We hypothesized that the omega-3 supplementation would reduce these adipokines after 10 weeks as well as TZD.

Materials and Methods

In the present double blind randomized controlled trial in 2013, 45 subjects of both sexes, 4065 yr old, tested and diagnosed with diabetes mellitus by physician, were enrolled during appointments at the Iranian Diabetic Association Center in Tehran, Iran. Fort four participants successfully completed the study. The inclusion and exclusion criteria are listed in Table 1. Randomization was carried out using a random permuted block. All participants (45 T2DM) were randomized to the following groups based on BMI: 1) 23 type 2 diabetic patients constituted the case group; and 2) 22 T2DM patients served as the control group. The two homogeneous groups were prescribed four capsules of omega-3 fatty acids or four capsules of placebo per day. To avoid possible adipokines and progesterone level changes in the luteal phase, premenopausal female patients were asked to begin treatment in the early follicular phase of their menstrual cycles. All participants were requested to maintain their usual exercise and dietary habits. …

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