Finucane OM, Lyons CL, Murphy AM et al (19 authors).
Monounsaturated fatty acid-enriched high-fat diets impede adipose NLRP3 inflammasome-mediated IL-1β secretion and insulin resistance despite obesity.
Diabetes. 2015 Jun;64(6):2116-28. doi: 10.2337/db14-1098. Epub 2015 Jan 27.
Saturated fatty acid (SFA) high-fat diets (HFDs) enhance interleukin (IL)-1β-mediated adipose inflammation and insulin resistance. However, the mechanisms by which different fatty acids regulate IL-1β and the subsequent effects on adipose tissue biology and insulin sensitivity in vivo remain elusive. We hypothesized that the replacement of SFA for monounsaturated fatty acid (MUFA) in HFDs would reduce pro-IL-1β priming in adipose tissue and attenuate insulin resistance via MUFA-driven AMPK activation. MUFA-HFD-fed mice displayed improved insulin sensitivity coincident with reduced pro-IL-1β priming, attenuated adipose IL-1β secretion, and sustained adipose AMPK activation compared with SFA-HFD-fed mice. Furthermore, MUFA-HFD-fed mice displayed hyperplastic adipose tissue, with enhanced adipogenic potential of the stromal vascular fraction and improved insulin sensitivity. In vitro, we demonstrated that the MUFA oleic acid can impede ATP-induced IL-1β secretion from lipopolysaccharide- and SFA-primed cells in an AMPK-dependent manner. Conversely, in a regression study, switching from SFA- to MUFA-HFD failed to reverse insulin resistance but improved fasting plasma insulin levels. In humans, high-SFA consumers, but not high-MUFA consumers, displayed reduced insulin sensitivity with elevated pycard-1 and caspase-1 expression in adipose tissue. These novel findings suggest that dietary MUFA can attenuate IL-1β-mediated insulin resistance and adipose dysfunction despite obesity via the preservation of AMPK activity.
This was a complicated and expensive piece of work, with no obvious COIs:
The work presented in this article has been supported by Science Foundation Ireland http://dx.doi.org/10.13039/501100001602 (grant SFI PI/11/1119). The CORDIOPREV and LIPGENE study subjects and investigators were funded by European Commission FP6 (grant FOOD-CT-2003-505944).
So has it been designed in such a way that it can tell us anything reliably about the effects of fats in human diets?
- The mice are C57BL/6 so get fat on diets that may not fatten humans, and the diet is 45% fat, 35% CHO which is half sugar, plus casein. Trisun oil vs Palm oil used means PUFA was well-controlled. However, it also means we're looking at a particular type of SFA - palmitate and stearate - versus the generic MUFA oleic acid that's prolific in every fat, even the palm oil here.The mice fed more MUFA gained less weight than the mice fed SFA. Is this plausible? It's consistent with Delaney et al (2000). However, this same evidence would predict that, had the SFA source been coconut oil, then the SFA mice would have gained less weight than the MUFA mice.
- Second human study (LIPGENE) compares effect of MUFA intervention in high-SFA people living in Scandanavia with same intervention in high-MUFA people living in Italy. Again, SFA/MUFA was determined by plasma levels. Even apart from this, I think there could be a few confounders within this arrangement that were not discussed in the paper. Results are shown in supplementary figure 6 here.
Interestingly, there is no discussion whatsoever of limitations vs strengths of the research in the paper.
Does this mean the results are wrong? Many studies show that MUFA is associated with better insulin sensitivity than SFA in high-carb diets, but the difference seems to disappear at higher fat intakes.
[Edit 1/4/16: the science for this is much less convincing than I was given to believe. Most studies show no difference. The KWANU study only showed a non-significant difference which disappeared at 47% fat. The effect is only seen in humans, when it is seen, with differences in fat type that are outside the normal range obtained in people freely choosing fatty foods, in other words at the same extra-physiological concentrations of the various fatty acids that are produced in the mouse studies.]
The mouse study "demonstrated that enrichment of obesigenic HFDs with MUFA can improve insulin sensitivity, reduce adipose IL-1β–mediated inflammation, and promote adipose hyperplasia compared with diets enriched with SFA". Promoting adipose hyperplasia might not be something everyone wants. A possible explanation is that more fat storage in subcutaneous adipose tissue (and somewhat higher rate of oxidation) from MUFA in the obesigenic diet results in less visceral and ectopic fat - the former (VAT) is more inflammatory than subcutaneous fat, the latter (ectopic fat in liver and pancreas) results in insulin resistance and type 2 diabetes. But because of the mouse model used, this doesn't answer the question, what is an obesigenic diet in humans? The C57BL/6 mouse can't tell us what happens in humans if MUFA replaces carbohydrate instead of replacing SFA, but we have human studies showing that, e.g.
"As compared with the high-carbohydrate diet, the high-monounsaturated-fat diet resulted in lower mean plasma glucose levels and reduced insulin requirements, lower levels of plasma triglycerides and very-low-density lipoprotein cholesterol (lower by 25 and 35 percent, respectively; P less than 0.01), and higher levels of high-density lipoprotein (HDL) cholesterol (higher by 13 percent; P less than 0.005)."
 Borghjid S, Feinman R. Response of C57Bl/6 mice to a carbohydrate-free diet
Nutrition & Metabolism 2012;9:69
 DeLany, JP, Windhauser, MW, Champagne, CM, Bray, GA. Differential oxidation of individual dietary fatty acids in humans. Am J Clin Nutr October 2000;72(4): 905-911
 Volk BM, Kunces LJ, Freidenreich DJ et al. Effects of step-wise increases in dietary carbohydrate on circulating saturated fatty acids and palmitoleic acid in adults with metabolic syndrome. PLoS One. 2014 Nov 21;9(11):e113605. doi: 10.1371/journal.pone.0113605. eCollection 2014.
 Sattar N, Gill JMR. Type 2 diabetes as a disease of ectopic fat? BMC Medicine 2014; 12: 123
 Garg A, Bonanome A, Grundy SM, Zhang ZJ, Unger RH. Comparison of a high-carbohydrate diet with a high-monounsaturated-fat diet in patients with non-insulin-dependent diabetes mellitus. N Engl J Med. 1988 Sep 29;319(13):829-34.