Ovide-Bordeaux S, Grynberg A. Docosahexaenoic acid affects insulin deficiency- and insulin resistance-induced alterations in cardiac mitochondria. Am J Physiol Regul Integr Comp Physiol, 2004; 286: R519-R527.

The effect of docosahexaenoic acid (DHA) intake on cardiac mitochondrial function was evaluated in permeabilized fibers in insulin deficiency and insulin resistance in rats.

The insulin-deficient state was obtained by streptozotocin injection 2 mo before investigations. Insulin resistance was obtained by feeding a 62% fructose diet for 3 mo.

DHA was incorporated in the diet to modify the fatty acid composition of cardiac membranes, including mitochondria.
Insulin deficiency decreased mitochondrial creatine kinase (mi-CK) activity and mitochondrial sensitivity to ADP.

DHA intake prevented these alterations. Moreover, the insulin-deficient state significantly decreased n-3 polyunsaturated fatty acids (PUFA) and slightly increased n-6 PUFA in both cardiac and mitochondrial membranes, inducing a significant increase in the n-6-to-n-3 ratio.

DHA intake maintained high myocardial and mitochondrial DHA content.

Insulin deficiency also decreased glutamate- and palmitoylcarnitine-supported mitochondrial respiration, but DHA intake did not prevent these effects.
In contrast, insulin resistance did not affect mi-CK activity or sensitivity to ADP.

However, insulin resistance influenced the myocardial fatty acid composition with decreased n-6 and n-3 PUFA contents and increased monounsaturated fatty acid content.

Only slight alterations were observed in mitochondrial fatty acid composition, and they were corrected by DHA intake. Moreover, insulin resistance decreased the glutamate-supported respiration, and DHA intake did not influence this effect.

In conclusion, the impairment of cardiac mitochondrial function was more pronounced in the insulin-deficient state than in insulin resistance. The modification of fatty acid composition of cardiac and mitochondrial membranes by DHA partially prevented the mitochondrial alterations induced in the two models.

Winnicki M, Somers VK, Accurso V, et al. Fish-Rich Diet, Leptin, and Body Mass. Circulation, 2002;106:289-291.

Background Leptin has been implicated in cardiovascular disease. A diet rich in fish has been associated with decreased cardiac and vascular risk.

Methods and Results We examined the relationship between diet and leptin in 2 related homogeneous African tribal populations of Tanzania.

One tribe consumes freshwater fish as their main diet component (n=279), and the other tribe consumes a primarily vegetarian diet (n=329).

In multivariate analysis, plasma leptin levels were associated with type of diet (F=14.3, P<0.001), independent of age, body mass index, body fat, alcohol consumption, or insulin.

Both male (2.5±2 [fish diet] versus 11.2±2.4 [vegetarian diet] ng/mL, P=0.017) and female (5.0±1.9 [fish diet] versus 11.8±1.4 [vegetarian diet] ng/mL, P=0.007) fish eaters had lower plasma leptin levels than did their vegetable diet counterparts, even though body mass index values were virtually identical.

Conclusions A diet rich in fish is associated with lower plasma leptin, independent of body fat.

These findings may have implications for understanding the reduced cardiovascular risk in subjects on a high-fish diet.

Fish Oil Helps Prevent Diabetes. Presented at the Annual Experimental Biology 2002 Conference New Orleans, LA April 21, 2002

NEW ORLEANS (Reuters Health) - An omega-3 fatty acid found in fish oil appears to improve insulin function in overweight individuals who are vulnerable to type 2 diabetes, researchers report.

Three months of daily supplementation with docosahexaenoic acid (DHA) produced a "clinically significant" improvement in insulin sensitivity in overweight study participants, according to Dr. Yvonne Denkins, a nutrition researcher at the Pennington Biomedical Research Institute, Louisiana State University in Baton Rouge. She presented the findings here Saturday at the annual Experimental Biology 2002 conference.

More than 9 out of 10 diabetics have the type 2 form of the disease, where the body's gradual failure to respond to insulin can cause blood sugar levels to rise to dangerous levels.

Previous population studies have suggested that fish oil might help protect against diabetes. "There were epidemiological studies on the Greenland Eskimos, a population of people that eat mainly whale blubber," Denkins pointed out. "These are people that are overweight, that should be diabetic and have heart disease, but they do not. The scientists that studied them thought it was probably because of what they eat, and they found that it was the omega-3s."

In their study, Denkins and colleagues had 12 overweight men and women, aged 40 to 70, consume 1.8 grams of DHA at breakfast for 12 weeks. While none of the study participants had full-blown diabetes, they all suffered from insulin resistance--a pre-diabetic condition in which the body fails to efficiently respond to insulin.

Using blood tests taken at the start and end of the study, the researchers assessed changes in each person's insulin resistance.
"We did see a change in insulin sensitivity after 12 weeks of DHA supplementation," Denkins told Reuters Health. A full 70% of the study participants showed an improvement in insulin-related function, she said, "and in 50% it was a clinically significant change."

Denkins stressed that the small size of the study sample means that the results remain preliminary, and diabetics should never replace their medications with any dietary supplement, including fish oil. Individuals considering upping their intake of fish oil should also consult their doctor beforehand, especially if they a re being treated for any cardiovascular condition, she added. This is because DHA has a slight blood thinning effect.

Nutrition experts currently recommend a daily intake of 0.6 grams of omega-3 fatty acids, preferably from fish. According to Denkins, that works out to about two servings of cold-water fish--species like halibut, herring, mackerel or salmon--per week.

Source: E. J. Mundell, Pennington Biomedical Research Institute, Louisiana State University in Baton Rouge, Experimental Biology Conference, 2002.

Borkman M, Storlien LH, Pan DA, et al. The Relation between Insulin Sensitivity and the Fatty-Acid Composition of Skeletal-Muscle Phospholipids. NEJM, 1993; 328(4):238-244.

Background
Insulin resistance and hyperinsulinemia are features of obesity, non-insulin-dependent diabetes mellitus, and other disorders.
Skeletal muscle is a major site of insulin action, and insulin sensitivity may be related to the fatty-acid composition of the phospholipids within the muscle membranes involved in the action of insulin.

Methods
We determined the relation between the fatty-acid composition of skeletal-muscle phospholipids and insulin sensitivity in two groups of subjects.
In one study, we obtained samples of the rectus abdominis muscle from 27 patients undergoing coronary artery surgery; fasting serum insulin levels provided an index of insulin sensitivity.
In the second study, a biopsy of the vastus lateralis muscle was performed in 13 normal men, and insulin sensitivity was assessed by euglycemic-clamp studies.

Results
In the patients undergoing surgery, the fasting serum insulin concentration (a measure of insulin resistance) was negatively correlated with the percentage of individual long-chain polyunsaturated fatty acids in the phospholipid fraction of muscle, particularly arachidonic acid (r = -0.63, P<0.001); the total percentage of C20-22 polyunsaturated fatty acids (r = -0.68, P<0.001); the average degree of fatty-acid unsaturation (r = -0.61, P<0.001); and the ratio of the percentage of C20:4 n-6 fatty acids to the percentage of C20:3 n-6 fatty acids (r = -0.55, P<0.01), an index of fatty-acid desaturase activity.
In the normal men, insulin sensitivity was positively correlated with the percentage of arachidonic acid in muscle (r = 0.76, P<0.01), the total percentage of C20-22 polyunsaturated fatty acids (r = 0.76, P<0.01), the average degree of fatty-acid unsaturation (r = 0.62, P<0.05), and the ratio of C20:4 n-6 to C20:3 n-6 (rho = 0.78, P = 0.007).

Conclusions
Decreased insulin sensitivity is associated with decreased concentrations of polyunsaturated fatty acids in skeletal-muscle phospholipids, raising the possibility that changes in the fatty-acid composition of muscles modulate the action of insulin.