Obesity does not cause metabolic syndrome; insulin resistance causes obesity. True?

I have already discussed my concerns about whether obesity is a disease or not and here we have another attempt of Dr Lustig to make the obesity irrelevant, pronouncing it as only an associated factor with the metabolic syndrome (MetS). He believes that not obesity causes insulin resistance but that insulin resistance causes obesity. He also believes that it is only the abdominal fat (inside the abdomen) that is a factor for the insulin resistance development whereas the subcutaneous fat is not the cause of anything.  

I agree that fat deposits in different body parts represent a different risk of metabolic diseases. However, does that make the excess subcutaneous fat irrelevant, so that we could ignore the obesity and focus only on the MetS features? I doubt so. 

Just a recap: 80% of obese people still suffer metabolic diseases (that is 4 out of 5) and as Dr Lustig said, so does the 40% of those having a 'normal weight'. However, about 50% of these 'normal weight' are actually overweight. So, is the obesity and excess adiposity under the skin really irrelevant? What percentage of these overweight would actually suffer metabolic issues in contrast to those really of a normal weight? 

Dr Lustig insists that firstly there is an insulin resistance, leading to leptin resistance, which leads to obesity and when this insulin issue is fixed, then the leptin issue is fixed, and then the obesity will be fixed as well: 

Because:

You know what? I AGREE with that. Partly. People tend to develop metabolic issues as they are becoming overweight and obese. In this mechanism it is really difficult to distinguish to what extent it is a marker (due to wrong diet and lifestyle) and to what extent it is a cause. Meanwhile, it is individual for each person WHEN and at what level of excess adiposity they will qualify for the diagnosis of MetS.

Just think: if people were not constantly in a positive energy balance for weeks and months - would they develop metabolic disturbances? Would they get high cholesterol, high blood pressure, would they become insulin resistant, because the muscles cannot take any more energy molecules in? I bet that most of them would not and as you may be aware, in many people, who reduce their body weight, their metabolic markers also improve. Slim people do not tend to suffer metabolic syndrome at such a large scale as obese and overweight people do. 

Should we therefore dismiss the link between obesity and metabolic diseases just because some thin people become ill and 1 in 5 obese does not?

Dr Lustig made it clear: people develop metabolic diseases irrespectively of the excess of subcutaneous body fat and he did it via this slide: 

He said that insulin resistance is what the obesity and lipodystropy have in common. However, you might have already read my objections against using this lipodystrophy case. It was because these people are genetically predisposed for insulin resistance which makes them too different from the rest of us. In addition, these familial partial dystrophy cases are rare. In the nutshell, the lipodystrophy means abnormal distribution of body fatness and represents a group of various diagnoses that are characteristic with lipodystropny. People are either genetically predisposed or they acquire this condition as a consequence of other condition such as being HIV positive and treated with various medication of having a history of autoimmune disease. 

The lipodystrophy is a specific condition and is rather rare in comparison to the prevalent overweight and obesity cases which mostly occur due to simply overeating and having low levels of physical activity. People suffering from lipodystrophy are often overeating due to leptin deficiency, while overweight and obese people become leptin resistant due to constantly positive energy balance, often leading to insulin resistance, too. What they have in common is that both cases: lipodystrophic and obese people have disturbed metabolism of energy. However, there is difference: 

• lipodystrophic people are unable to store fat in some body parts (under the skin in limbs), but  they can store it in other body parts (neck, face, around the organs), which makes them to look slim, but in fact they are metabolically ill and obese inside. The inability to store fat under the skin and excess adiposity in other places affects the whole endocrine system, sometimes also leading to overeating, which further worsens the condition. This is what Dr Lustig has been describing. Nonetheless, the whole condition is caused by some other condition, as mentioned above. Overeating is a consequence of reduced subcutaneous fat tissue and low leptin levels and the insulin resistance develops as a consequence of this.
• obese people, on the other hand, usually develop metabolic disturbances as a consequence of simply consuming too much energy, (or unhealthy diet as such, this is a broader topic) while they were initially healthy and metabolically normal. They become insulin resistant and as such, because the elevated insulin interferes with leptin receptors of hypothalamus, they also become leptin resistant as a consequence. And so they continue eating like they did from the time when they were slim, because they love food, it is cheap, plenty of it and unaware of its energy content. And the leptin resistance does not make them stop even if they have increased leptin concentrations in blood. Therefore the mechanism is the opposite than in people suffering various forms of lipodystrophy. 

Therefore, in my opinion, this example of lipodystrophy should not have been used to disprove the link between the body fatness and metabolic diseases in the population not affected by the lipodystrophy.

The Reframing the debate slide ended with this: 

Does this disprove the close link between excess body weight (or the process of gaining weight) and various features of metabolic syndrome? I do not think so. I see this initiative as messing around because at the end, there will again be FRUCTOSE. 

Going back to The Reality image, I have already highlighted that the metabolic dysfunction cannot be the cause of obesity for people who are metabolically normal and start to gain weight because of the obesogenic environment. And you could see that I gained weight without the symptoms of the metabolic disturbances just because I enjoyed the palatable and fattening foods too much and did not bother to move to burn the extra energy. I halted this trend when I reached BMI 27+ but if I did not do so I would most likely follow the fate of my close family who suffer a whole spectrum of metabolic dysfunctions, including obesity, hypertension, high cholesterol, cardiovascular diseases, fatty liver, type 2 diabetes, etc. I currently suffer none of these as a result of my lifestyle, I never did and I hope I will successfully avoid such conditions in the future. 

What Dr Lustig was talking about were his obese patients who struggled to lose weight because of having their biochemistry already affected for various reasons: hypothalamic trauma, specific genetic condition, being obese for some time already, unhealthy lifestyle, etc.

What I am saying is that although for many people the insulin resistance makes them to fail losing weight, but for them to gain weight firstly the insulin resistance is not a necessary factor. It tends to work the other way around: as people are gaining weight, they become insulin resistant in the process of gaining weight or when they finally become obese, because having this extra amount of fat in the body is not healthy at all. 

Oops, he did it again - presenting two different premises and using one as a proof for the other.

In the past you could see Dr Lustig turning the traditional perception of the obesity development upside down. He said that it was not due to the behavior, when people reach for energy dense food and prefer to stay physically inactive because they can. It rather was the sole role of biochemistry that drove the behavior of people to overeat, remain sedentary and gain weight. He even strengthened this premise by pointing at obese 6 months old, probably expecting that all cases of obesity should be explained by exactly the same mechanism.

Another cases he used to support this biology driven reason for obesity were his patients after suffering a hypothalamic trauma. The hypothalamus of these people could not read the leptin which would otherwise stop them eating when full and preventing them to store extra adipose tissue. But because this mechanism was not working in these people, as a result of overeating they developed insulin resistance, which further drove the metabolic diseases, associated with obesity. As a proof that the obesity can only be fixed from the inside, Dr Lustig demonstrated how he managed to fix it by artificially reducing the release of insulin first by using a drug and then watching how the patients started to lose weight and even enjoy the physical exercise. And, as a proof that this has the effect on people without the hypothalamic trauma, he demonstrated this on another patient who was just being obese, proving himself right in his point. He also illustrated this mechanism on an example of two children receiving a cookie: a slim child became hyperactive but an obese child did not, because it was leptin resistant, most likely due to the hyperinsulinemia as a result of insulin resistance. But how they become hyperinsulinemic in the first place? 

We should look back when it all started. I mean the individuals without the hypothalamic trauma or leptin receptors deficiency, which are the majority of obesity and metabolic disease cases worldwide. Before they developed insulin and leptin resistance they were perfectly metabolically healthy, but the wrong dietary and lifestyle choices made them gradually overweight, obese and metabolically sick. They did not express the gluttony and sloth before but they have developed them after wrong dietary choices and a prolonged time of positive energy balance. Dr Lustig never discussed this order of events properly. Even when elaborating on how the food industry and the lack of effective policies promote these unhealthy choices, it was not about the unhealthy choices themselves in his argumentation other than our likeness for sweet taste, which fructose provides in foods. The blame was always put on somebody else, never on the individuals that actually made those choices and put the food items into their mouths. What is more, Dr Lustig constantly focuses on already diseased people how powerless they are under their condition and applies their conditions and ill metabolism on the healthy people as if the origins of the consequences were identical among these people. 

As you have noticed by now, Dr Lustig illustrated that it was not the behavior that drove obesity levels in his patients suffering a hypothalamic trauma.  When thinking about the differences, I have realised that these patients were firstly resistant to the leptin present in their bodies and then they started to eat like crazy, storing excess fat and slowly developing insulin resistance. In other cases, without this trauma, it is either the regular spikes of insulin that makes the hypothalamus less responsive to leptin, or gradually developing the insulin resistance (most likely due to the constant positive energy balance), that makes them leptin blind. These are two different premises. However, Dr Lustig constantly pictures the later stages of obesity development or gradually developed insulin resistance as a cause of obesity or metabolic diseases. He uses a mechanism of consequence as a mechanism of cause in these people without the hypothalamic traumua. WHY? I suspect he is biased by his medical profession where he mainly treats symptoms rather than looking at the cause of the problem in its nature and since his fructose agenda become a worldwide thing he tries to adjust other physiological mechanisms to fit this proposed frame. 

I have a different opinion. 

In the video from which is the following slide, Dr Lustig uses the same tactic again. In order to dismiss the generally perceived and accepted adipocentric model of the metabolic syndrome development (and insulin resistance within), he used an extreme case such as familial partial lipodystrophy. This is a result of a serious genetic mutation and you can see on the patient that he is not quite like the rest of us: 

The patient was genetically predisposed where he stored and did not store the extra fat, or rather from which body regions the affected people start losing the subcutaneous fat as they mature and age. Although we all have this differentiated fat storage places - we store extra fat on our hips, stomach, arms, but not too much on palms of hands, on our ear lobes or hair area - people like this patient are too different from the most of us due to having other metabolic problems including 'inability to properly breakdown a simple sugar known as glucose (glucose intolerance), elevated levels of triglycerides (fat) in the blood (hypertriglyceridemia), and diabetes'.

What that means? The patients with this genetic condition do not develop metabolic diseases despite of not storing fat under their skin but because of their genetic susceptibility for them, in addition to the gradual loss of subcutaneous fat. In fact, the inability to store potentially excess energy intake in the subcutaneous fat depot can actually contribute to their metabolic disturbances. 

So this was another inappropriately used supporting example by Dr Lustig proving NOTHING about the allegedly non-existent causal link between the excess subcutaneous adipose tissue and metabolic health of the average population. And, as one researcher (M. Constantine Samaan from McMaster University) pointed out when I discussed the origin of insulin resistance: 

"One other organ to be considered is the brain. Evidence from animal models suggests that high fat diet causes animals to become insulin resistant prior to weight gain, and that this is the result of hypothalamic inflammation. Whether this applies to human MetS is unknown."

So here you have two different views on the origin of insulin resistance in relation to hypothalamus. Can the high fat diet be a culprit of hypothalamic insulin resistance in normal people, making them leptin resistant and subsequently develop obesity? Remember that insulin is also a hormone regulating food intake: hypothalamus reads increased glucose and a subsequent insulin release as a sign of food intake and Dr Lustig agreed with this as well. 

But the insulin resistance in hypothalamus is not the same as overall body hyperinsulinemia. Read more about why we might be hyperinsulinemic today here. 

Now, how fructose comes into this? Almost 100% fructose is metabolized by the liver, only micromole concentrations appear in blood whereas glucose appears in millimole concentrations, a thousand times higher amount. Can liver cause all these problems? Read more about this issue here.