Are marine n-3 fatty acids protective towards insulin resistance? From cell to human

Abstract

Marine n-3 fatty acids improve most of the biochemical alterations associated with insulin resistance (IR). Experimental models of dietary-induced IR in rodents have shown their ability (often at a very high dose) to prevent IR, but with sometimes a tissue specific effect. However, in a high sucrose diet-induced IR rat model, they are unable to reverse IR once installed; in other rodent models (dexamethasone, Zucker rats), they are inefficacious perhaps because of the severity of IR. The very low incidence of type-2 diabetes (T2D) in Inuits in the 1960s, which largely increased over the following decades in parallel to the replacement of their traditional marine food for a western diet strongly suggests a protective effect of marine n-3 towards the risk of T2D; this was confirmed by reversal of its incidence in intervention studies reintroducing their traditional food. In healthy subjects and insulin-resistant non-diabetic patients, most trials and meta-analyses conclude to an insulin-sensitising effect and to a very probable preventive or alleviating effect towards IR. Concerning the risk of T2D, concordant data allow us to conclude the protective effect of marine n-3 in Asians while suspicion exists of an aggravation of risk in Westerners, but with the possibility that it could be explained by a high heterogeneity of studies performed in this population. Some longitudinal cohorts in US/European people showed no association or a decreased risk. Further studies using more homogeneous doses, sources of n-3 and assessment of insulin sensitivity methods are required to better delineate their effects in Westerners.

Long-chainn-3 PUFA given before and throughout gestation and lactation in rats prevent high-fat diet-induced insulin resistance in male offspring in a tissue-specific manner

“…As expected, and after 6 weeks on HF diet, the glycemic and insulinemic responses and the NEFAs plasma levels were higher in HF than in C dams, reflecting glucose intolerance and IR of both glucose metabolism and lipolysis. These alterations were not observed in HFn-3 rats, confirming their preventive effect towards IR in rodents as reported in many studies (14) . Although higher in HFn-3 than in C dams, plasma leptin concentrations were lower in HFn-3 than in HF dams, related to a probable lower fat mass and/or reduced leptin expression in AT as previously observed (43,44) .…”

“…In rodent models, a high fat diet (HF) rich in saturated fatty acids (SFAs) given during pregnancy induces several metabolic alterations in offspring during adulthood: liver steatosis, increased body and visceral fat mass, adipocyte hypertrophy, pro-inflammatory cytokines production, IR, pancreatic islet hypertrophy, and oxidative stress (11,12) . Long chain (LC) n-3 PUFAs, mainly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) can prevent and even decrease IR in rodents fed a HF diet, which has also been shown in humans (13)(14)(15)(16)(17)(18) . During pregnancy, the only source of PUFAs for the developing fetus is via the placenta.…”

Fish oil minimises feed intake and improves insulin sensitivity in Zucker fa/fa rats

“…An alleviation of liver lipotoxicity, as previously observed in rats and mice fed a high-fat diet (1,(40)(41)(42)(43)(44)(45)(46) , has also probably contributed to the alleviation of liver IR in our study. It must be noted that in our study we did not explore these molecular mechanisms, in particular fatty acid oxidation.…”

“…Long-chain n-3 PUFA (LC n-3 PUFA) have repeatedly demonstrated to partially or completely prevent insulin resistance (IR) in rodents as well as in humans, but contrasting effects have been observed in both species (1,2) . In rats, they can prevent IR induced by a high-fat, a high-sucrose or a highfructose diet (3)(4)(5) .…”