Hi Pianoman - on a basic level, it's not premature to be drawing conclusions, provided the conclusions are justified by the data. It's a bit early for the papers to be saying that high fat diets cause diabetes, without a shadow of a doubt, but that's a journalistic problem, not a scientific one.
As far as I can tell they did also supplement some mice with directly added (i.e. not dietary) palmitic acid, an FFA, and saw a similar response but not as pronounced. The mice on the high (trans)fat diet had higher FFA levels than the mice on the high carb diet or the added FFA ones.
I'm not sure about not knowing that a high fat, hypercaloric diet causes obesity (or at least in mice) - they fed mice a high fat diet that was hypercaloric and the mice became obese. Other mice were fed a lower calorie, higher carb diet and didn't. I go back to my earlier point that there are other ways of becoming obese, but excess calories and high fat intake do seem to do it.
I agree that the intake levels differed significantly - all that suggests though is that trans fats are not directly harmful in themselves, but they are in high quantities. I don't think that's particularly novel.
A connection between diet, obesity and diabetes exists in multiple species and is the basis of an escalating human health problem. The factors responsible provoke both insulin resistance and pancreatic beta cell dysfunction but remain to be fully identified. We report a combination of molecular events in human and mouse pancreatic beta cells, induced by elevated levels of free fatty acids or by administration of a high-fat diet with associated obesity, that comprise a pathogenic pathway to diabetes. Elevated concentrations of free fatty acids caused nuclear exclusion and reduced expression of the transcription factors FOXA2 and HNF1A in beta cells. This resulted in a deficit of GnT-4a glycosyltransferase expression in beta cells that produced signs of metabolic disease, including hyperglycemia, impaired glucose tolerance, hyperinsulinemia, hepatic steatosis and diminished insulin action in muscle and adipose tissues. Protection from disease was conferred by enforced beta cell–specific GnT-4a protein glycosylation and involved the maintenance of glucose transporter expression and the preservation of glucose transport. We observed that this pathogenic process was active in human islet cells obtained from donors with type 2 diabetes; thus, illuminating a pathway to disease implicated in the diet- and obesity-associated component of type 2 diabetes mellitus.
http://www.nature.com/nm/journal/vaop/ncurrent/full/nm.2414.html
The experimental conclusions that I read from this are that a) they fed some mice a high (trans)fat diet and the mice became obese. b) These obese mice had high levels of FFA. c) these levels interfered with the mice's ability to regulate glucose and insulin. d) mice fed a high carb, lower calorie diet didn't have either the increased FFA or inmpaired response. e) mice with induced levels of FFA not via diet also had a similar response, but not as strongly. I think the phrase 'illuminating a pathway to disease' is clear that they are not suggesting that this is a direct causal link or the only link.
the only real claims they are making are:
Elevated concentrations of free fatty acids caused nuclear exclusion and reduced expression of the transcription factors FOXA2 and HNF1A in beta cells. This resulted in a deficit of GnT-4a glycosyltransferase expression in beta cells that produced signs of metabolic disease, including hyperglycemia, impaired glucose tolerance, hyperinsulinemia, hepatic steatosis and diminished insulin action in muscle and adipose tissues. Protection from disease was conferred by enforced beta cell–specific GnT-4a protein glycosylation and involved the maintenance of glucose transporter expression and the preservation of glucose transport
Pianoman: Surely if the cause is diet, then why reach for a patent-able and profitable solution rather than a simple dietary intervention?
I don't think they are saying the (only) cause is diet. I think the paper is fairly clear that diet plays a part, genetics play a part but other factors unknown are involved. The actual genesis of the test seems to be that they noticed mice with a defect in the GnT-4a glycosyltransferase encoded by the Mgat4a gene had a version of T2. They assumed that GnT-4a plays an important role in glucose regulation and wanted to test that.