by Bill Roberts
Gene Expression, Nutrient Partitioning, and Leanness
The right training and supplement can help move your body weight set point, making it easier to get lean or build muscle.
Whether you call it a set point or a homeostasis point, it’s the same thing: your body tends to remain in about the same state. Bodyweight is one example.
It seems like a casual statement, but actually it’s a powerful thing. For example, let’s compare three people who eat and exercise identically:
- One might naturally stay at about 200 pounds in fairly lean condition. It would take substantive changes for his body to move far from this in either direction.
- The second person – eating and training the same way as the first – might tend to stay at about 220 with 40 pounds more fat than the first guy.
- The third person might struggle to reach a soft 180 on equal training and diet.
Different genetics might be the explanation. But sometimes it clearly isn’t. What if we were talking about the same individual at different points in time? Then genetics couldn’t be the explanation. Or at least not genetics in the usual sense of having a particular DNA code.
It’s Not Just Genetics
Often a person can improve set points of body weight, muscle mass, and body fat – independent of changes in training or nutrition – simply by being persistent with his or her current workouts.
A novice whose body tended strongly to remain at a soft 180 might easily become a 200-pound lean lifter in three years of training, even on the same macronutrient intake and training volume. His muscle gene expression adapted to support a higher set point for lean mass, and his adipose gene adapted to create a lower set point for fat mass.
It’s important to note that macronutrient intake often doesn’t stay the same. A more experienced lifter may stay muscular while consuming less protein and calories than he did earlier when having a much lower set point for muscle. Or he might consume more calories yet remain leaner. These examples show that diet isn’t the sole determinant.
Your set points can also get worse. Many find it far harder to maintain a condition that was easy for them 10 or 20 years previously. It’s easy to blame aging, but that’s a very vague explanation, and it’s not necessarily the cause of the problem. Plus, that explanation provides no solution.
But what if you improved gene expression? Now that can be a solution.
What Are Set Points Really?
Set points can be simple or complex. It’s simple enough to notice that your body tends to stay at some given weight, while at another time, it may have tended to stay at some different weight. And it’s simple enough to notice that if you don’t control calories your body fat tends to stay at a particular amount.
But let’s take a closer look: There’s no known way in which the body measures your weight and adjusts its processes to maintain that number. Instead, staying a particular weight results from many aspects of gene expression.
Of these aspects, the most important are those which control nutrient partitioning, adipose inflammation, and skeletal protein muscle synthesis i.e., muscle building.
Nutrient Partitioning: Key to Muscle and Leanness
I was first introduced to the idea of nutrient partitioning back in the 1990s from Dan Duchaine’s writings. He was huge on this point and on aspects of it, such as insulin sensitivity.
I have to admit that I really didn’t get it. With correct weight training and a reasonable diet, wouldn’t your muscles grab the nutrients they need in any case? If you want to lose fat, don’t you just need to reduce calories to less than you burn, regardless of nutrient partitioning?
Wasn’t that just a basic fact? To lose fat, eat less. Eat more than you burn and you’ll gain fat. That was about it.
Well, I was wrong. In fact, it’s enormously different being where your body regulates itself to be lean and stays lean (unless you really pig out for an extended time) versus being where your body regulates itself to be fat, and you have to kill yourself to get lean.
Meet Muscle Mike and Fat Fred
How does nutrient partitioning control leanness? To help you understand, let’s make an analogy.
Mike and Fred both work at a remote outpost. A plane drops a food package every day for the both of them to divide as they will. It has suitable protein, carbs, and fat for two people.
Fred’s a fat and lazy guy. Mike is muscular, does all the work around the place, and trains with weights.
What happens if Mike insists, “I do all the work around here, so I’ll take what I want and you pick up the scraps?” Mike’s nutrient intake will then support his weight training and work. He may gain muscle mass. As for Fred, he may lose fat.
But what if Fred grabs as much food as he wants instead, beating Mike to the plate? Mike’s likely to lose muscle mass and body weight, while Fred gets even fatter.
In either case, the fellow receiving only leftovers would be getting enough nutrition to survive. Even if it went on for years, he wouldn’t die; he’d simply stabilize at a lower body weight. Mike and Fred’s set points would be determined by who grabbed food first and how much that person tended to leave for the other.
In this analogy, Mike is your muscle and Fred is your fat. And “who grabs the food first” is your nutrient partitioning.
Vicious Cycle: Adipose Inflammation, Insulin Sensitivity, and Fat Mass
One of the main factors controlling nutrient partitioning is your insulin sensitivity, and even more specifically, the difference in insulin sensitivity between your muscle and fat cells. If you improve your nutrient partitioning, your body’s set point changes from supporting mostly body fat to supporting mostly muscle.
Insulin sensitivity is strongly related to adipose inflammation and amount of body fat. It’s a vicious cycle:
- Impaired insulin sensitivity causes the body’s set point for fat mass to increase. That means the person will gain fat unless great and consistent care is taken.
- The resulting increased fat mass yields increased adipose inflammation.
- The increased adipose inflammation yields worsened insulin sensitivity, further ramping up the cycle.
Worse, many other adverse changes in gene expression occur in concert with the increase in body fat. It’s a hard cycle to break.
One answer is to just bite the bullet and lose the fat, as hard as that is to do when impaired gene expression already exists. Many have done it successfully, but far more have tried and failed or had only temporary success. A key reason for this is that after about 10% of body weight has been lost, losing even more typically slows metabolism. Some succeed despite this; many do not.
Even among those who succeed, many find themselves in a metabolically impaired situation where they can’t consume as many calories as others, can’t handle a normal carb intake, and can’t build or maintain as much muscle mass while remaining lean. All this is from gene expression.
Exercise and Gene Expression
What sorts of exercise will change your set point towards a leaner physique?
Rather than rely on biochemistry, rely on the findings of successful coaches, on the accounts of those who have followed the plans, and personal experience. But as it happens, biochemistry completely backs up what they’ve found.
And while weight training is one of the most effective ways to improve your set point, many don’t lift in an effective manner for that purpose. Are you short-changing yourself?
Brief, intensive exercise with hypertrophy-range weights taken to maximal effort will bring cellular energy levels low (or specifically, convert most of the cell’s ATP to AMP) and drive cellular oxygen levels low.
If tension is kept constant when lifting, blood flow is largely occluded. And if rest periods are kept short relative to the workload, muscle temperature increases. (About 104° F appears optimal.)
All these things improve gene expression for fat burning and elevated metabolic rate as well as muscle growth.
Does this sound like Christian Thibaudeau’s Growth Factor Training? Or even like Vince Gironda’s classic physique-transforming methods? It should. It also sounds like high-intensity interval training (HIIT), and it should.
Coaches have long said to train this way, but frankly, it’s hard. Many pump their reps, lose tension at the top or bottom of reps, do more sets of easier work, and allow too much rest time between sets. Or they do exclusively heavy work for low reps, which always leaves considerable cellular energy reserves. If you want to reset your physique to be naturally lean, don’t train like that.
Modulate Your Gut Bacteria for a Leaner Set Point?
Yes, your gut bacteria can have a profound effect on your set point for body fat. Unfortunately, presently available probiotics won’t help much. For now, be aware that there’s indeed a great relevance, and for now, a good diet is your best way of favorably modulating your gut bacteria.
Could a Supplement Create A Leaner Set Point?
Can we change gene expression towards fat loss without inducing metabolic impairment, or even better, while improving metabolism? Yes. Among the gene expression changes we’d want are:
- Reductions in inflammatory IL-6, IL-1β, and TNF-α
- Reduction in inflammation-promoting TLR-4 and MCP-1
- Increase in anti-inflammatory adiponectin
- Increase in GLUT-4 to increase nutrient transport into muscle
- Increase in metabolic-rate-speeding uncoupling proteins
As a consequence of gene expression changes, we’d like to see proof of reduced systemic inflammation as shown by reduced C-reactive protein, and lower response to LPS, a fat-promoting endotoxin produced by some of the normal gut bacteria.
And, of course, we want to see results in practice where people’s set points improve dramatically! Too much to ask for? Not at all.
Cyanidin 3-Glucoside (C3G) Creates A Leaner Set Point
C3G, sold as Indigo-3G (Buy at Amazon), is always described in terms of the effects people see for themselves. Improved gym performance, improved muscle gain, improved fat loss, and – for those with impaired ability to handle carbs – improved carb tolerance.
What’s rarely discussed is Indigo-3G’s origin. Why did Biotest ever decide to research cyanidin 3-glucoside, at doses never before tried?
Part of the answer is gene expression. Cyanidin 3-glucoside was clearly the most potent available nutritional agent for favorably modulating gene expression. Every mechanism I discussed above, cyanidin 3-glucoside (the active anthocyanin in Indigo-3G) is proven able to do.
You lose body fat on Indigo-3G (Buy at Amazon) not because of receptor stimulation (as with typical “fat burners”) but because your set point becomes one of lower body fat for your given diet and exercise level. The effect remains even on discontinuance.
Natural, Sustained Leanness
Focusing your efforts on improved gene expression – through better diet, better exercise, and better supplementation – is the way to natural, sustained fat loss. Change your set point to a favorable one rather than push endlessly against an unfavorable set point.
