We are not obese, we are inflamed!
Sushant Kumar
Founder-Genefitletics|IEAlumni|Built Asia’s first disease detect platform to early detect metabolic diseases & cancer|Transforming human biochemistry into molecular data platform|Biohacking & Longevity
Abstract
Over the last 10 years, obesity has skyrocketed with Calorie in-calorie out becoming the narrative & guiding principle to curb weight gain & obesity
As such we have seen a number of startups in weight loss space, whether it is institutionalized or trainer/coach led, propagating this narrative as the solution for weight gain woes.
However still the number of people developing this metabolic syndrome has increased more than ever with close > 40% of Indian population is either overweight or obese
Needless to mention, calorie in- calorie out is not an absolute measure- no brainer right & current solutions are shooting in the dark with 0% accuracy
While there is no doubt that energy balance is the key for optimal weight management, it never translates to only a “ calorie in-calorie out” strategy.
Human biology is the most complex machinery & three major factors program our biology for health or disease. Without understanding & measuring each of these aspects, any such fad diets or coach led weight loss models leaves huge blank space.
-Our biology is as unique as our fingerprint, necessitating our unique responses to various external factors
-Our biology is sack of tens of thousands of biochemical reactions which works in synchrony to keep our body in homeostasis
-99% of our biology & these biochemical reactions are governed by our microbiome that constitute 99% of genes expressed inside our body & > 50% of cellular ecosystem.
If people will do well enough to read scientific journals backed by research & empirical evidence, they would find it hard to avoid the role of microbiome in healthy weight management. Unfortunately, current weight loss solutions are nothing but a financial model with non-scientific interventions.
The way forward
Let us discuss science behind health weight management & role of microbiome
1)Biochemical way how microbiomes influence weight management: The food you eat is a sack of thousands of molecules. When you consume a meal, you are ingesting tens of thousands of molecules. Microbes in your mouth are the first one to interact with these molecules & pre-process them so that it is readily available for absorption. While some of the molecules get absorbed in the upper digestive tract, a lot of them reach your gut where microbes sense each of these molecules & express particular genes that code for proteins that transform( absorb) these molecules into chemicals. This essentially means your microbes translate these molecules into nutrients, neurotransmitters, hormones, vitamins or into toxins & harmful metabolites. These bioactive compounds secreted by your microbiome influence most of metabolic activity & have impact on weight management
2)Gut microbiome is an organ- immune modulator energy regulator: When your gut microbiome is balanced & you are feeding them with right food substrates, they could transform them into beneficial chemicals/metabolites which regulates your satiety, blood sugar response & regulate your metabolic activity & more. Some of these metabolites include
a) Butyrate(Butyric acid): Certain microbes in your gut could synthesize inulin, dietary fiber & other beneficial prebiotics into Butyrate which not only strengthens the gut lining but also improves satiety & gives you a feeling of fullness. This automatically regulates your energy balance by sending biochemical signals telling you that you have had enough & your biology does not need any additional nutrients or calories right now. Butyrate also reduces the level of inflammation & thereby influencing healthy weight management given the fact that low grade chronic inflammation is a contributor towards weight gain(1) .
Please remember everything is not about calories & butyrate is biochemical signaling molecule. Those trainers or fitness companies who say butyrate is not important as it does not offer calories, need to do a reality check & deep dive into science rather than living in their own dreamy world.
b)Propionate: Similar to butyrate, propionate contributes to satiety & reduces inflammation
c)Acetate: This microbial derived metabolite is responsible for modulating production of insulin. High insulin levels lead to fat storage. Excess acetate produced by gut microbes signals to stimulate insulin secretion, resulting in weight gain(2)
3.The key culprit- Inflammation: When you have microbial dysbiosis which is nothing but your microbes expressing virulence genes based on their interaction with external environment( nutrition, stress, toxins, air), they could secrete inflammatory metabolites that could make it hard for you to lose weight. Some of inflammatory metabolites include
a)TMAO: You might be consuming too much of protein for specific gut microbes- Proteobacteria that may ferment specific amino acids into harmful amines such as trimethylamine(TMA) & other amines. TMA released in the blood stream is transported to the liver where it is oxidized into TMAO. TMAO triggers pro-inflammatory responses, leading to increased fat storage & reduced fat export(3)
b)LPS: Your gut microbiome synthesizes sugar & processed foods into lipopolysaccharides(LPS) which stimulates immune response & leads to adipogenesis & adiposity, causing weight gain & making you fat. Gut dysbiosis over time causes leaky gut which allows LPS to translocate into the bloodstream & rent out space in other body organs, triggering a wave of system inflammation( fun fact: This is one of the endotoxin that causes type 2 diabetes). Late night binge eating causes microbial circadian stress & certain microbes may feel they are getting attacked by other microbes & in order to protect themselves they release an endotoxin called (LPS). This LPS is potent poison & is implicated not only in onset & progression of obesity & type 2 diabetes.
(These are few obesity causing metabolites, there are number of others that triggers adiposity)
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4.The gut brain axis love affair: Gut & brain communicate via vagus nerve by sending & receiving various biochemical signals. This communication influences how often you feel like refuelling your biology via neurotransmitter signaling. Many neurotransmitters are produced in the gut & infact microbes may be sending signals to brain, sending a requisition for more food or telling that you are full.
You may have certain microbes active that are greedy & always craving for food via
-Microbes could influence ghrelin, leptin & other peptides involved in energy expenditure so that you may feel hungry when you shouldn’t(4).
-If you do not have enough butyrate producing microbes, it could directly impact gut-brain control of satiety regulation
-Microbes can impact expression of certain hormones such as GLP-1, PYY that regulates your satiety via release of digestive enzymes(5)
5.The Gut-thyroid connection:It is no brainer that underactive thyroid function is connected with weight gain. Gut microbiome stimulates activity of TSH- Thyroid Stimulating Hormone which promotes production of two hormones- T3 & T4. The human body can only use the T3 hormone & hence T4 has to be converted into T3 for our body to use them. The microbes in the gut influences activity of the iodothyronine deiodinase enzyme which is responsible for this T4 to T3 conversion. Part of this conversion is also attributed to availability of Selenium & Zinc which again depends upon how well our gut microbiome metabolizes & synthesizes these nutrients
The success of this process also depends upon the production of bile acids in our gallbladder. When this bile acid is secreted into the small intestine, our gut microbiome metabolizes & synthesizes it into secondary bile acids which impacts the activity of iodothyronine deiodinase enzymes.
Therefore if your gut microbiome is imbalanced, it can disrupt the production of TSH & can lead to underactive thyroid leading to weight gain(6)(7)
6.Oral microbiome-the neglected organ in weight management(8):Microbes living in our mouth have been ignored for too long. While the scientific community & specific biotech companies have been too much driven to understand gut microbiome, it has now been found that salivary microbiome not only impacts our oral health but has downstream impact on our metabolic health including the onset of obesity.The oral microbiome could make you gain weight via
a)Oral-Gut Axis: Gut & oral share at least 75% of microbiome & via saliva which we swallow daily( around 1 liter). Certain microbes from the mouth translocate to gut. These microbes could express virulence gene which could lead to systemic inflammation, adiposity & influence eating behavior( gut-brain axis)
b)Oral-blood axis:Translocation of oral microbes in blood stream, due to excessive inflammation which causes leaky gums, leads to systemic inflammation & adiposity which in turns changes the taste & food preference, leading to weight gain
To summarize, weight gain & obesity is an outcome to multitude of biochemical functions taking place inside the body & just using calorie deficit as the only means to weight loss is a lost battle.
We have all the scientific literature & evidence in place that establishes the deep rooted connection between inflammation & weight gain. Please read them & become scientifically aware rather than falling for claims made by these fitness influencers & weight loss companies. Sharing a few citations below. Next time, if anyone is trying to convince you that calorie in-calorie out is the only way to reduce weight, please show them these research papers.
All the best
Citations
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1moThank you for sharing Sushant Kumar