Falling Down

New evidence indicates that the body can sense gravity, and by manipulating the sensors we can trick our metabolism into losing fat while retaining muscle. The modern diet makes this mechanism less effective, and Covid lockdowns have made matters even worse; but there are nutritional work-arounds which enhance fat loss and protect our joints at the same time. 

The Covid lock-downs have been ruinously expensive. They have hit the world economy hard, shrinking it by roughly 6%, killing jobs and plunging many into poverty (1). They have led to increased suicides, marital breakdowns, spousal and child and drug abuse, and have probably caused more deaths than covid itself (2-4). And they have not been particularly effective in containing Covid (5).

We can now see that the real Covidiots are the politicians who, despite the early semi-controlled Diamond Princess and Gangelt data sets which showed that Covid was not a serious public health issue (6-8), used it as an excuse to reduce our freedoms and increase theirs. But it is the long-term effects of lockdown that will be the most expensive, and the most destructive.

A third of the global population aged ≥15 years is already insufficiently physical active. This contributes to approximately 3.2 million deaths every year by increasing obesity, diabetes, cardiovascular diseases, osteoporosis, cancer, cognitive decline (9, 10) and early death (11).

Americans already spend 7.7 hours a day seated (12). When lockdown forces folk to shelter and work at home, sitting down goes up to 11.7 hours a day (13, 14). 

This has made an already astonishingly fat nation, fatter. About half the population have gained weight, by an average of 29 lbs (14). It’s a similar story in other countries which have gone the lockdown route (145-23).

This is doing enormous damage to our health prospects, damage which will continue long after the current crop of political covidiots have been thrown out of office and onto the ash heap of history. But you don’t have to be a victim. You can take control over your own life – and you can start by standing up, and walking. 

Walking from the couch to the fridge doesn’t count. Sorry. To protect your health, stand up every hour or so and climb a couple of flights of stairs, or do 10 minutes of stretches, or both (24).

Muscular exertion activates the muscle enzyme lipoprotein lipase (LPL), which helps to keep your blood lipids under control. It also activates the energy switch AMP-kinase, of which more later. Aim for a minimum 25-30 minutes / day of moderate physical activity (25).

Switch to a low-cal anti-inflammatory diet if you can. Next, add gravity. Not Gravity, the tedious Bullock / Cluney vehicle – you’re trying to cut down on couch time, remember? I mean gravity, the kind you can feel.

Consider sense and sensibility. Mystics and Janeites claim that we have as many as 53 senses (26). Neuroscientists claim a more conservative 9, which starts with the basic 5 and adds thermoception, nocioception, proprioception and equilibrioception. Very recently, a tenth sense has been added to the list; the sense of weight, or gravity. And it may be the key to losing those lockdown love handles.

When lab rats or mice are weighted down with lead pellets they lose substantial amounts of weight (27, 28). This is almost exclusively adipose tissue. Unlike dieting, there is little if any loss of muscle mass (27-29), making lead an ideal weight loss strategy for the lazy. The Gothenburg researchers who did this work postulated a body weight regulating mechanism which worked in parallel with the leptin system, and called it ‘the gravitostat’. 

They reproduced the experiment in a clinical trial, which generated the same result (30). Their paper concludes, ‘Increased weight loading reduces body weight and fat mass in obese subjects in a similar way as previously shown in obese rodents. These findings demonstrate that there is a loading-dependent homeostatic regulation of body weight, the gravitostat, also in humans.’

I must add that an Oregon team which actually shot a colony of rats into space decided that the gravitostat didn’t exist, and suggested that weight loss in the Swedish mice was due to injury and/or stress (31). The Oregonians were seemingly unaware of the Swedes’ successful clinical trial (30) and the science is not yet settled; but at the time of writing I think the Gothenberg group (and another at Columbia U) outweighs them (32, 33).

The concept of a gravitostat raises some interesting questions. If the gravitostat actually exists, in which tissue or tissues is it located? What does it consist of? How does it work? Can it be manipulated by a molecule that you could, perhaps, put in a pill?

If I were to design a gravitostat I would place it in or around the knee joints because the higher in the body you locate such a sensor, the less able it is to respond to total body weight. When your legs are not in use (ie when you sit down) it would be disabled. This is one reason why sitting makes you fat – and is so bad for your health (34-36). 

There is some experimental evidence for a leg or knee-based gravitostat. 

Previous work with mice in low-gravity models showed that de-loading the hind limbs leads to loss of muscle (37) and bone (38), while increased loading has the reverse effects (38). These effects are mediated by the mechano-transducer cartilage protein Piezo1 (39), making Piezo1 a plausible weight sensor in the still theoretical gravitostat; and an exercise sensor also (40-42). 

Piezo1 has a broader role. 

In bone Piezo1 senses load and torque, and is involved in bone maintenance and growth in response to exercise (43). In the arteries it senses shear and stretch, and is a sensor in the homeostatic regulation of blood flow whenever requirements change (44). It guides the growth of tissues from embryogenesis onwards (45), and basically allows higher life forms to respond to the constantly changing physical demands of living in the material world (46). 

If Piezo1 is a sensor, what is/are the effectors? The sestrins are prime candidates, as they are stress-responsive and activate AMP-kinase (47), which preferentially burns adipose tissue while conserving lean muscle mass (48).  However, the sestrins are autocoids, and act very locally unless there is a general up-regulation of sestrins in multiple muscle groups. 

Standing and walking about under normal (Earth) gravity is probably enough to achieve this. Upping the G-force by wearing 20 kg of lead weights on your back should activate even more AMP-K, increase your BMR and lose body fat – which is what the Swedes demonstrated. For evolutionary reasons, increased loading would be expected to burn fat rather than the muscle needed to carry the increased weight, so the idea seems plausible.

There are additional reasons to put on a full metal jacket. Unloading the hind limbs (ie sitting too much) damages the metabolism and the miocrobiome (49). Due probably to the reduction of stresses in the extra-cellular matrix, it also degrades the machinery of apoptosis (50) in ways which slow wound healing and increase the risk of clinical cancer (51). 

These mechanisms are relevant to astronauts and to couch potatoes too (ie 52) who are, in physiological and metabolic terms, sub-orbital astronauts. And all of them would be switched off by amping up the G’s, and loading up with lead. But why is the gravitostat not triggered by ‘normal’ weight gain, I hear you ask?

I believe the gravitostat evolved to respond to relatively acute changes in loading such as the sudden and repetitive 4-fold increased loading of the knee which occurs when running (53, 54). Excess weight is heavily penalized in the wild because it makes you more likely to transition from predator to prey and disappear from the gene pool; and I can say, from personal experience, that running makes you lose weight fast.

The gravitostat fails in the modern world because we are excessively sedentary, and it is not designed to respond to gradual increases in weight which take place over months and years. It adjusts, in the same way as baroreceptors do to the slow development of essential hypertension – which you will acquire, along with adiposity, if you eat the modern, ultra-processed diet. And as adiposity degrades cartilage in weight-bearing joints (55), it may degrade the gravitostat too.

Now we come to a crunch. Can the gravitostat be triggered by nutritional components? The answer is, probably yes.

The polyphenol resveratrol protects against the damaging effects of de-loading by acting as an exercise mimetic (56); and does so by activating AMP-K directly (57). Other nutrients which do the same thing include the polyphenol quercetin (57), the sapogenin dammaranes (58), and the omega 3 fatty acid EPA (59).

Dietary intakes of all these protective compounds declined dramatically after the nutrition transition (60), and have fallen further as a result of lockdown. Many people have switched to comfort (aka junk) foods, which are depleted in polyphenols, saponins and EPA.

The ultra-processed diet is also deficient in prebiotic fiber, leading directly to dysbiosis; and all of these nutritional gaps interact with the enforced sedentarism to damage the gravitostat (61) and weight-bearing joints in general (61). They also make people fatter, sicker and more vulnerable to Covid (ie 62, 63).

Politicians are not scientists, and in my experience they rarely think of second order effects other than those which benefit them personally. Politically motivated lockdown is probably the most egregious error in public health of all time (64). It has made the general population more likely to die of Covid (64-68) and more vulnerable to future pandemics, which will come.

In the next post. Why the spectrum disorders are increasing, how to protect your unborn baby’s brain, and why I am such a rude and objectionable person.

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