Body Fat Biochemistry: Optimized

Body Fat Biochemistry: Optimized Part II Dr. Lonnie Lowery

Okay, we’re back at this fat biochemistry thing. Check out Part One to find out the important consumer protection – and body fat control – reasons for staying up on this stuff! Gurus all have their little “systems”, books often over-emphasize a single aspect of weight control as their “reader hook”, and YOU are still left wondering why the heck you’re still not ripped. Let’s continue not only learning about fat regulatory pathways, but how you can tweak the ones that might be the missing link to your leanness stalemate!

Sex hormones: Generally we think about muscle tissue when this bodily system comes up but fat loss is also controlled. Since T is known to facilitate subcutaneous fat loss over time – and even combat the effects of belly fat-inducing cortisol - maybe we can just jack-up the T. This sounds logical but is under classic negative-feedback (homeostatic) control like other pathways and bodily systems. We all know that increased T concentrations in the blood (which tend to aromatize into E2) reduce LH levels and eventually even shrink testicular size. This leaves a choice for the high-Test individual: prevent aromatization into E2 with (possibly more) drugs or block the resulting E2 at the receptor level with something like tamoxifen. Yet even these approaches won’t fool Mother Nature indefinitely.

Optimize this System: The long-term alternative approach is to nudge-up endogenous free-T concentrations gently and perhaps cyclically, coinciding with annual physique goals. There are supplemental approaches to this (e.g. chasteberry [“vitex”] – it’s even in teas, eurycoma [“longjack”], green oat extracts [avena sativa], and combinations like Tribex, Alpha Male, etc.), dietary maneuvers like increasing fat intake and maintaining steady overall food intake,(2, 5, 12) and even behavioral/ training-ritual ways to raise T, as Rob Fortney and I discussed on our recent Experiments vs. Experience CD. Aggressive facial expressions and music just scratch the surface. It’s also a possibility that during “down cycles” when we give our androgen levels a rest, the hormonal focus can change to decreasing cortisol secretion (as opposed to blocking its effects with T). This is possible with reduced coffee/ caffeine intake,(13, 14) small frequent meals,(11) adequate protein intake,(7) – even meditation and fish oil consumption as I’ve explored in my Blog.

But back to upping the T. This whole sex hormone approach to fat reduction is much like fat loss from an energetic perspective: Coax it with patience and understanding of genetic limitations rather than pull a rash attempt to force-out some instant gratification. (Read as: avoid abusing self-administered androgens). Like all good things, truly screaming T can’t – and shouldn’t - last forever.) Homeostasis will see to it that you swing the other way, ultimately, and no one wants to pay for four weeks of androgenic hardness with eight weeks of smallness and softness.

ASP: Ah, another Medline surfers’ obsession. Is the acylation-stimulating protein (ASP) just lots of hype or the main determinant of body fat? Yes, this fat cell-derived protein does indeed do what its name implies: it stimulates fat uptake from the blood, with subsequent creation of triglyceride (fat) storage. (Yuck! Even if we admit that we can’t leave blood lipids mucking up our arteries either.) So, as with other body fat control pathways, there is valid evidence behind it.(3, 8, 9, 26) But like the others, it doesn’t always pan-out on a whole-body systemic level that matters to a physique-focused person. First off, fat transport mechanisms are at work other than ASP.(16, 23) Second, dropping ASP too much could well leave fat lingering in our blood vessels; for example, trans fats lower ASP but they are recognized as detrimental to our blood lipid profile.(15)

Further, depending upon one’s interpretation, a study by Ozata and colleagues (2001) suggests that other systems supercede ASP in their ability to impact body fat. The researchers improved blood sugar control (with sulfonylurea drugs) in some obese, Type II diabetic subjects, with resulting decreases in body mass index, waist and hip girth. This sounds good and is predictable, based on what I’ve seen in my limited clinical exposure. This leaning-out, however, was in the face of a 50% rise in ASP! To me, this suggests that ASP may not be the end-all, be-all fat regulator that sends Medline surfers into a tizzy. If ASP is the primary culprit in the drawing-in and assembly of body fat, how is it that these obese subjects got leaner in the face of much greater ASP levels? Despite a link between the two (1), at least during this study’s duration, it looks like the Adkins pundits are right in blaming insulin action, not ASP per se, as the major factor regarding America’s fat loss woes. Just some food for thought.

Optimize this System: Of course, I still don’t want ASP raging in my body, so keeping dietary fats lower, early in the day (which keeps down circulating chylomicrons that regulate ASP activity; [9]) is helpful. A controlled fat intake helps keep this pathway in check but as we mentioned under the Insulin Section, we can’t rely entirely on carbs as a fuel source either. Again, we’re back to moderation and variety, as with AM carbs, PM fats and protein throughout. Want to get more specific? The T-Dawg 2.0 Diet is a reasonable way to approach these issues. It’s also my favorite “diet” available on this site.

Inflammatory cytokines: Is body fat just a result of inflammation?! Well, immune system substances like pro-inflammatory cytokines certainly play a role.(8, 27) The link between obesity and low-grade inflammation is well known. In fact, controlling it can even improve glucose tolerance – which we’ve seen to have a strong impact on body fatness. As an illustration, high-dose aspirin (NOT recommended) can actually decrease (i.e. improve) blood glucose 20%!(10) This is not to say that aspirin is an anti-obesity drug but it does do some mildly-supportive things regarding fat reduction. More specific to pro-inflammatory cytokines, we don’t want things like tumor necrosis factor and interleukin-6 running wild on us. This is even more of a muscle preservation concern than it is a fat loss one.

Optimize this System: About a half-liter of dilute carb drink during exercise goes a long way to keep undesirable cytokines at bay. And if you wait until 10-20 minutes into a session, insulin elevation won’t slow-down your fat loss attempts, either! There’s also the nearly omni-present fish oil approach, which can lower pro-inflammatory cytokines as well.

Note that we’re optimizing what we’ve got, not “fixing” anything per se. Don’t blame me, blame your parents. Environment is the largest contributor to body fat but any environmental change you institute will still interact with available genes. Genes influence (but don’t dictate) our hormones and biochemical pathways. The whole process is so complex, it’s no wonder that permanent long term weight and fat loss greater than 10% below baseline are nearly impossible. A cold scientific statement might describe this fact as “redundant body weight protective pathways” or for slightly older guys: “a midlife thrifty phenotype”. Okay, that’s nice for a starving or older caveman in mid-winter but it sucks for many modern people trying to see their abs. Fortunately, all these genes, pathways, systems and hormones also offer multiple approaches to optimizing body composition.

Here’s an old endocrine class epiphany… ALL HORMONES AND PATHWAYS ARE SOMEHOW RELATED! Just as the “new” trend in weight training is to treat the body as a functional, flowing unit rather than isolated muscles, it’s also true that our biochemical systems are interconnected and flowing rather than isolated. So before anyone asks how to tweak / improve any of these specific pathways beyond what I have explored here, let me just make a blanket statement: 1.) Run 2.) Lift 3.) Eat with variety and moderation in mind. Moderation includes about 35% fat by calories in the diet; new research continues to suggest that when we eat fat, we teach the body to burn fat.(28) Just don’t eat too much at one time; 50g is pushing the “burn it vs. store it” metabolic balance.(21) I’m sorry if that’s to mundane but these three principles will have a greater impact on body fat mass, and thus all these pathways, than micromanagement of any single pathway or system via overdoses of a particular nutrient or by way of a “proprietary system”. Watch for gimmicky diet gurus capitalizing on this stuff. We still need to see how each of these approaches to body fat pans out. One thing laboratory and medical exposure teaches is that homeostasis rules the day. Treat one bodily system and others will compensate accordingly, leaving any tunnel vision fat loss efforts fruitless.

But back to our earlier statement, applied knowledge is indeed power and each person, despite the same basic physiology, “presents” with different fat-related etiologies (i.e. has different causes for fatness and responds to different treatments). Working with someone who understands the BIG PICTURE and corrects for failed approaches by trying new things is helpful. Just beware overly excited sales pitches from non-clinically trained gurus or diet book and supplement companies telling you that a specific pathway is the reason for your love handles. It may sound logical but logical does not always mean physio-logical!

Print off and arm yourself with this article if you choose to shell out hard-earned dollars to a sports nutrition/ weight loss guru. Or if you’re getting hooked on a given book. If you are confronted with reams of babbling biochem, let the guru know that you’re already clued-in to how no single pathway is all-determining when it comes to body fat and function.

LEARN MORE: If you’d like to hear more tips, research and opinion from Dr. Lowery, you can order his dietary supplement review/book chapter, co-authored with John Berardi, at www.lifestyleschanges.com (use discount code ‘LON’ for 5% off the text), see him at the October 31st Boot Camp in Las Vegas with Charles Staley (www.myodynamics.com), or get his audio seminar on CD, "Experiments vs. Experience, Vol. 1", by checking out http://www.geocities.com/lonman07/E-vs-E.html.

References and Further Reading (Parts I and II):

1. Ahren, B., et alo. Acylation stimulating protein stimulates insulin secretion. Int J Obes Relat Metab Disord. 2003 Sep;27(9):1037-43. 2. Booth, A., et al. Endogenous testosterone and competition: the effect of "fasting". Steroids. 1993 Aug;58(8):348-50. 3. Cianflone, K., et al. Critical review of acylation-stimulating protein physiology in humans and rodents. Biochim Biophys Acta. 2003 Jan 31;1609(2):127-43. 4. Considine, R. Regulation of leptin production. Rev Endocr Metab Disord. 2001 Oct;2(4):357-63. 5. Dorgan JF., et al. Effects of dietary fat and fiber on plasma and urine androgens and estrogens in men: a controlled feeding study. Am J Clin Nutr 1996 Dec;64(6):850-5. 6. Gabrieli, I., et al. Hyperglycemia induces PAI-1 gene expression in adipose tissue by activation of the hexosamine biosynthetic pathway. Atherosclerosis. 2002 Jan;160(1):115-22. 7. Groschl, M., et al. Endocrine responses to the oral ingestion of a physiological dose of essential amino acids in humans. J Endocrinol. 2003 Nov;179(2):237-44. 8. Guerre-Millo, M. Adipose tissue hormones. J Endocrinol Invest. 2002; 25(10): 855-861. 9. Havel, P. Control of energy homeostasis and insulin action by adipocyte hormones: leptin, acylation-stimulating protein, and adiponectin. Curr Opin Lipidol 2002; 13(1): 51-59. 10. Hundal, R., et al. Mechanism by which high-dose aspirin improves glucose metabolism in type 2 diabetes. J Clin Invest. 2002 May;109(10):1321-6. 11. Jenkins, D., et al. Nibbling versus gorging: metabolic advantages of increased meal frequency. N Engl J Med 1989 Oct 5;321(14):929-34. 12. Lambert CP, et al. Macronutrient Considerations for the Sport of Bodybuilding. Sports Med. 2004;34(5):317-327. 13. Laurent, D., et al. Effects of caffeine on muscle glycogen utilization and the neuroendocrine axis during exercise. J Clin Endocrinol Metab. 2000 Jun;85(6):2170-5. 14. Lovallo, W., et al. Stress-like adrenocorticotropin responses to caffeine in young healthy men. Pharmacol Biochem Behav. 1996 Nov;55(3):365-9. 15. Matthan, N., et al. Hydrogenated fat consumption affects acylation-stimulating protein levels and cholesterol esterification rates in moderately hypercholesterolemic women. J Lipid Res 2001; 42(11): 1841-1848. 16. McCarty, M. Modulation of adipocyte lipoprotein lipase expression as a strategy for preventing or treating visceral obesity. Med Hypotheses. 2001 Aug;57(2):192- 200. 17. Muller, M., et al. Thermic effect of epinephrine: a role for endogenous insulin. Metabolism 1992 Jun;41(6):582-587. 18. Ozata, M., et al. Improved glycemic control increases fasting plasma acylation- stimulating protein and decreases leptin concentrations in Type II diabetic subjects. J Clin Endocrinol Metab 2001; 86(8): 3659-3664. 19. Rosenbaum, M., et al. Low dose leptin administration reverses effects of sustained weight-reduction on energy expenditure and circulating concentrations of thyroid hormones. J Clin Endocrinol Metab 2002 May;87(5):2391-4. 20. Scroggie, D., et al. The effect of glucosamine-chondroitin supplementation on glycosylated hemoglobin levels in patients with type 2 diabetes mellitus: a placebo-controlled, double-blinded, randomized clinical trial. Arch Intern Med. 2003 Jul 14;163(13):1587-90.. 21. Sonko BJ., et al. Dose-response relationship between fat ingestion and oxidation: quantitative estimation using whole-body calorimetry and 13C isotope ratio mass spectrometry. Eur J Clin Nutr. 2001 Jan;55(1):10-8. 22. Thong, F. and Graham, T. Caffeine-induced impairment of glucose tolerance is abolished by beta-adrenergic receptor blockade in humans. J Appl Physiol. 2002 Jun;92(6):2347-52. 23. Turcotte LP. Role of fats in exercise. Types and quality. Clin Sports Med 1999 Jul;18(3):485-98. 24. Virkamaki, A., et al. Activation of the hexosamine pathway by glucosamine in vivo induces insulin resistance in multiple insulin sensitive tissues. Endocrinology. 1997 Jun;138(6):2501-7. 25. Weinberg, S. The diet-heart hypothesis: a critique. J Am Coll Cardiol. 2004 Mar 3;43(5):731-3. 26. Yasruel, Z. et al. Effect of acylation stimulating protein on the triacylglycerol synthetic pathway of human adipose tissue. Lipids 1991; 26(7): 495-499. 27. Yudkin, J., et al. Inflammation, obesity, stress and coronary heart disease: is interleukin-6 the link? Atherosclerosis 2000 Feb;148(2):209-14. 28. Zderic TW, Davidson CJ, Schenk S, Byerley LO, Coyle EF. High-fat diet elevates resting intramuscular triglyceride concentration and whole body lipolysis during exercise. Am J Physiol Endocrinol Metab. 2004 Feb;286(2):E217-25. Epub 2003 Oct 14.