This study looked at body weight, fat mass, blood lipid and glucose levels and PEPCK (rate limiting enzyme in glyceroneogenesis pathway for G3P production for esterification of fatty acids - fat deposition) activity in the liver and fat cells. Two ad libitum diets were compared, a control standard chow and a ketogenic zero carb chow. This study was in normal, young (30 days old at start) Wistar rats and lasted 6 weeks.
The diet compositions are shown below:
I've included this because in the past, the fat used in such diets has been PUFA or transfats so the results have been dismissed as due to the unhealthy fat content of the diets. In this case, however, the fat was mostly the "healthy fat" lard. Protein content was comparable by weight, though it would appear to be different by percent as carbs were apparently "swapped" for fat on a g-by-g basis.
So here were the results:
In the top plot we see that the KD rats gained less total body mass, but in the middle graph we see that they gained more fat (epididymal and perirenal fat = visceral fat in rats) leading to a significantly higher FM:TM ratio as shown in the bottom graph. I would note that not only is the ratio greater, but the trend was towards increasing the ratio as time went on and the slope of the trendline would indicate this worsens with time.
One thing this study shows is that glyceroneogenesis is perfectly capable of providing the G3P needed to deposit fat in the absence of dietary carb. PEPCK was elevated in fat cells (but not liver). The rats didn't become obese on this VHF diet, but they got fattier. This is that fuel partitioning that Taubes is now talking about as being how carbs make us fat because insulin makes fat accumulate. Only this shows just the opposite of Taubes' claims. It was the zero carb rats who partitioned more food calories to fat vs. lean mass. The insulin riddled rodents grew more, but partitioned their fuel towards lean mass. These results are similar to what was seen in mice following mild calorie restriction. Perhaps the carb restriction is sensed as "starvation" by the rats' bodies?
In any case, by the sixth week, the KD rats had accumulated 2.4X the fat mass than their carb and insulin ridden counterparts.
Interestingly enough in this study, the blood lipids were comparable (and the controls had higher HDL).
Not surprisingly, the KD rats had impaired glucose tolerance as determined by an intraperitoneal (injection into body cavity) glucose tolerance test. This was likely attributable to insulin resistance.
The authors describe the fat deposition as being "TAG saving activity" - in response to necessarily elevated FFA's, So the rats accumulate fat to maintain normal circulating lipids. I'm comforted to learn that ectopic fat deposition does not seem to occur with the ketogenic diets, however I'm not keen on visceral fat deposition! Perhaps this visceral "buffer" is the body's adjustment to greater lipid turnover in the "fat burning" metabolism.
In any case, this study and the results really flies in the face of the insulin-centric theories of obesity. Although the KD rats started to accumulate fat, they did not become obese, just fattier. The fat accumulation didn't spur overeating to continue the horizontal growth. The rats with reduced insulin and no dietary carbohydrate were more efficient "fat trappers" than those with the most insulin and a boatload of dietary carb.
The authors gave due diligence to the limitations of their study that I'll copy here:
It is important to mention some limitations and perspectives of this work. Firstly, the normal lipidemia observed does not necessarily reflect a normal storage or distribution. Moreover, most of the data available regarding PEPCK regulation are in rodents, thus elevated adipose glyceroneogenesis and its consequences deserve further investigation in humans.
Secondly, the visceral lipogenesis was accompanied by glucose intolerance. This apparent insulin resistance also has been reported in KD-fed rats subjected to insulin-induced hypoglycemia . On the other hand, an increase in insulin sensitivity has been described in children during KD . Thirdly, it is important to mention that KD is not prescribed ad libitum to children refractory to conventional anti-epileptic drug treatment. In fact, some authors have proposed KD with caloric restriction to investigate and to obtain the anti-epileptic effect of this diet . In our study, rats received ad libitum ketogenic or regular diet. Caloric restriction per se appears to induce an increment of hepatic PEPCK activity . Possibly KD with caloric restriction also increases adipose PEPCK activity. However, this issue also deserves further investigation.