Protein's Effects on Gene Expression: Higher Protein Lower Carbohydrate Diet Spares Gylcogen, Lowers Insulin and Reduces Lipogenesis

High protein diets have become the "gold standard" within the fitness community. On the countless bodybuilding, fitness and weight loss related bulletin boards on the Internet, athletes, gymrats and even overweight house-wives report outstanding benefits of a higher than normal protein intake on weight gain and/or fat loss. French scientists (Stepien. 2011) have now taken a closer look at the mechanism behind these success stories and found a strong (epi)genetic component (for an introduction to epigenetics, I recommend listening to Dr Rouse's interview series on Carl Lenore's Super Human Radio).

 Figure 1: Effect of high protein diet on genes regulating lipogenesis [lipo = fat; genesis = production] in the liver (Stepien. 2011)

Stepien et al. fed 80 male winstar rats either a normal or a high protein (50% protein) diet for 1,3,6 or 14 days and evaluated the mRNA levels [indicators of how active these genes are] of genes "involved in carbohydrate and lipid metabolism", energy expenditure (EE) and substrate oxidation, as well as liver glycogen, plasma glucose and hormones. What they observed stands in line with the positive anecdotal evidence you will find if you google muscle gain or fat loss "success stories":

    In liver, HP feeding 1) decreased mRNA encoding glycolysis enzymes (GK, L-PK) and lipogenesis enzymes(ACC, FAS), 2) increased mRNA encoding gluconeogenesis enzymes (PEPCK), 3) first lowered, then restored mRNA encoding glycogen synthesis enzyme (GS), 4) did not change mRNA encoding b-oxidation enzymes (CPT1, ACOX1, bHAD).

So, interestingly, with the exception of the 1st day of the experiment (where the increase in protein intake resulted in a short-term increase in fat oxidation), fat oxidation was stable (cf. 4) The "fat burning" effect, which is often ascribed to high protein diets, thus is not existent - or let's say its not a direct one, but a result of the synergy of other genetic and metabolic adaptations and the calorie restriction all weight loss regimens have in common.

Figure 2: Postprandial macronutrient balance as assessed during a 4 h period after the intake of a calibrated meal consisting of 4 g of an adequate diet.  (Stepien. 2011)

Here is where the insulin lowering effect, the reduced hepatic glucose uptake and the reduction in lipogenesis (cf. fig. 1) come into play. Combined with an overall increase in postprandial energy expenditure (observed only under long term high protein feeding conditions, cf. fig 2, HP14) and a slight but significant increase in the percentage of fat (LOX, fig. 2) that is used to fuel these demands, these genetic and metabolic adaption (most prominently the lower insulin levels and the reduction in lipogenesis) are the most probable mechanisms to explain the reduced fat gains and increases in fat loss on high protein weight gain and weight loss diets, respectively.