CLA for Lean Gains! Trans-10, cis-12 Conjugated Linoleic acid, But Not the Cis-9 Isomer, Decreases De Novo Lipid Synthesis in Human(!) Adipocytes by More Than 50%

Image 1: Most commercially available
products still have a mixture of the active
10,12 CLA and the inactive 9,11 CLA.

If you read the first installment of the SuppVersity Student Spotlight, and/or listened to our now famous SuppVersity student, Duong, on Carl Lenore's Super Human Radio, yesterday, you'll know that Duong's approach to intermittent fasting delivered impressive muscle gains, even on a caloric deficit! But what if you are lean already? Regardless of whether or not you fast intermittently, eating a hypocaloric diet (i.e. eating less calories than you need) does not appear to be the ideal strategy to "bulk", does it? Well, a group of international scientists from Denmark, the US, France and Germany recently found that CLA, or Trans-10, cis-12 Conjugated Linoleic Acid, to be precise, could possibly ward off fat gains by decreasing the amount of fat that is produced and getting stored in your adipose tissue (Obson. 2011).

Thomas Obsen and his colleagues found that incubation of cultured human adipocytes (human fat cells) with 30 μM 10,12 CLA, but not 9,11 CLA (the other of the two most abundant CLA isomers,

decreased de novo synthesis of triglyceride, free FA, diacylglycerol, cholesterol esters, cardiolipin, phospholipids and ceramides [from
[14C]-acetic acid and [14C]-pyruvic acid as substrates] within 3–24 h. [It also] decreased total cellular lipids within 3 days and the ratio of monounsaturated FA (MUFA) to saturated FA, and increased C18:0 acyl-CoA levels within 24 h.

With regard to the underlying mechanism, the scientists are quite certain that it was not "due to a 'structural trans effect'", because several other trans FA, the scientists used as controls "did not delipidate adipocytes or alter the MUFA/SFA ratio to the extent of 10,12 CLA".

Figure 1: Relative changes in de novo lipogenesis of triglycerides and free fatty acids in adipocytes incubated with either 9,11 or 10,12 CLA vs. control (data adapted from Obson. 2011)

 As an alternative explanation they propose that the anti-fat effects of CLA may be "due to the position of the trans double bond in the C18:2 structure of CLA." This would also be consistent with the experimental data (cf. figure 2), which shows that only 10,12 CLA, but not 9,11 CLA, suppressed de novo lipid synthesis within 3–24 h of treatment and cannot be explained by a lack of incorporation of 10,12 CLA, "as both CLA isomers [were] equally incorporate into lipids, albeit at lower levels than other unsaturated FA." The scientists go on to summarize their results as follows:

These and previously published data suggest that 10,12 CLA lowers the lipid content of adipocytes by (1) rapidly decreasing SCD-1 [enzyme responsible for mono unsatuarated fatty acid = MUFA synthesis] activity, thereby reducing the MUFA needed for neutral and compound lipid synthesis (reviewed in Ref. [34]); (2) decreasing PPARγ activity, thereby reducing the expression of adipogenic and lipogenic proteins needed for lipid biosynthesis; or (3) increasing inflammatory lipid metabolites or signals that antagonize glucose and FA uptake and subsequent metabolism.

In that, the results confirm the pro-inflammatory nature of CLA (whenever it "works") I have mentioned in previous blogpost. Chung et al. (Chung. 2005) and Kennedy et al. (Kennedy. 2010) have analyzed the inflammatory effect of CLA before and Obson et al. speculate that the "activation of inflammatory signals such as NFκB that antagonize LXRα, PPARγ and possibly also SREBP-1" could be the underlying mechanism which leads to "decreased activity of lipogenic enzymes essential for FA desaturation and incorporation into neutral and compound lipids within 3–24 h." This is of particular interest, because despite its effect on weight loss, the inflammatory component 10,12 CLA has could eventually turn against you, once overall inflammation passes a certain "healthy" threshold.

Figure 2: Rleative changes in adipocyte fatty acid composition after 3, 24, 72 and 216h of incubation with 9,11 CLA & 10,12 CLA vs. control (data adapted from Obson. 2011)

What's even more questionable, though, is in how far these in-vitro results will translate into real world weight loss. The most recent rodent trial (Arias. 2011) that used 10,12 CLA (0.3% of the diet) alone and in conjunction with resveratrol, for example, did find a modest reduction (-13%) in body fat gain in rats fed with a commercial obesogenic diet, i.e. a diet that is intended to trigger obesity in the animals. On the other hand, the effects of resveratrol (30mg/kg) were more profound and in combination, the two supplements canceled each other out. Thus, it is quite obvious that further research is necessary until we can say something about effective dosages and their respective weight loss effects... I guess I don't need to tell you that the SuppVersity is where you'll hear about these first ;-)