Metabolic Resilience: The Key to Maintain a Healthy Weight & Health? Part 2

Metabolic Resilience: The Key to Maintain a Healthy Weight & Health? Part 2


If you have not read part 1 yet, please do so to learn the definition and importance of metabolic resilience. I describe the first 2 of 5 factors: how stress and excess body fat (a condition called adiposopathy) play a role as stressors on our metabolism and ways to reduce those effects and build resilience.


Here, we cover the next 3 of 5 stressors on mitochondria health and in turn, effects on weight and metabolism.



1. Lack of physical activity:

A sedentary lifestyle trend has been steadily increasing in the general population as we spend more and more time seated at work, in vehicles and not moving. In particular as people age, they tend to move less. Does being sedentary have metabolic consequences at the mitrochondrial level?


This will get a little technical now.


Our muscles are made to move and adapt to our needs, by producing certain substances, called transcription factors. During physical activity, a signaling protein called AMP is increased, that leads to increased production of a protein called PGC1α (Peroxisome proliferator-activated receptor gamma coactivator 1-alpha).


Increased production of PGC1α results in improved mitochondrial ability to use the energy (food & stored energy) through turning on certain genes and improved lipid (fat) metabolism. The increased ability of mitochondria to use energy leads to improved insulin sensitivity (improved risk for type 2 diabetes, heart disease etc.).


In studies, sedentary people have been found to have decreased levels of PGC1α. Exercise also has been linked to boosted levels of NAD+ (discussed in next section), which is linked to improved cardiovascular health.

The beneficial effect of exercise is outside of other health benefits related to regular movement, including strength, flexibility, agility and “calories burned”.

How to Build Metabolic Resilience:

  • Move! Aim for 150 minutes every week of aerobic activity & 2 episodes of muscle resistance training


  • Consider “bursts” of activity like HIIT or interval training with studies suggesting increased visceral fat loss (inflammatory fat around the mid-section & organs) with such activity.


  • Find ways to move more daily- take the stairs, park further away, stand while you work, get up often and take a stroll. Avoid sitting for long periods of time.


2. Dietary stress (caloric overload):

Okay, let’s finally talk about effects of fasting, food, especially excess of highly calorically dense foods 24/7 in our society today…


Our nutritional status (over-fed vs restricted) affects mitochondria in our cells!


When our bodies are overloaded with food energy, the actual framework of the mitochondria changes and becomes more fragmented. This is a problem because ideally, we want mitochondria to be longer and interconnected so they are more efficient at using energy as fuel.


In mammals, when we have lots of nutrients present (a lot of food available), a protein called mTOR (mammalian target of rapamycin) is upregulated, which leads to growth and decreased time spent on cell repair. There is also inactivation of certain enzymes, affecting mitochondrial shape/size/number and activity. In rats, a high fat diet leads to impaired insulin sensitivity and overall metabolic flexibility is impaired.


Downregulating the mTOR pathway, along with reduced activation of a protein called Akt, leads to improved cell salvage pathways, or autophagy.


How can we downregulate mTOR and Akt?


Reduced caloric intake and fasting.


This leads to decreased insulin and IGF-1 (insulin-like growth factor-1), which in turn downregulate Akt. Calorie restriction also downregulates mTOR as well as upregulates another protein FOXO (forkhead box protein O) that lead to improved cell maintenance pathways that help with DNA repair and stress resistance.


We will also discuss below compounds called sirtuins- their role and how to potentially improve their activity in the body.


How to Build Metabolic Resilience:

  • This may sound obvious, but don’t eat to excess. Realize the consequences at the cellular level we just reviewed. And EAT REAL FOOD, not processed.


  • Practice fasting (overnight, we are all fasting!). Caloric restriction is the only physiological intervention that has so far been shown to increase lifespan in a range of species. Although this effect has mostly been proven in mouse models, we have seen it improves metabolic health and decline during aging. It’s not about counting every calorie- it is more about giving our body time periods for rest and repair. Our mitochondria & metabolism then get a chance to rebuild, repair and renew.


  • Increase dietary intake of foods that boost sirtuins(there are 7 known SIRT proteins). Sirtuin-activating compounds boost activity of enzymes that have been found to have effects on artery plaque formation and cardiovascular disease, metabolic syndrome/diabetes, and aging. At the physiological level, sirtuins impact inflammation, cell growth, circadian rhythms, energy metabolism, neuronal function, and stress resistance


  • Sirtuins are thought to mimic effects of fasting and calorie restriction and have beneficial cardiometabolic effects. An example of a sirtuin boosting substance is Reservatrol. In animal & human studies, reservatrol has had variable effects based on study population. A study on men with obesity and diabetes did find reduced body fat and improved glucose. In animal models, reservatrol has been found to improve mitochondria function and metabolism in diet-induced obesity, improved insulin resistance, aging and healthspan.


  • Examples of foods with polyphenols like reservatrol: grapes, apples, blueberries, plums, peanuts. A supplement dose is not yet clear but studies are ongoing.


  • Increased intake of NAD+ boosters- NAD+ is a prevalent molecule in the body, that is in close interaction with sirtuin proteins and a co-factor in many chemical reactions in our bodies. Compounds that boost NAD+ activity are being studied that are thought to have beneficial effects on blood pressure, cholesterol and arterial stiffness. NAD+ is made in the body from tryptophan as well as vitamin B3 (niacin).


  • Food sources high in niacin that help boost NAD+ are: Liver, chicken breast, tuna, salmon, peanuts, avocado, brown rice, mushrooms, green peas, potatoes.


  • In general, boost your intake of fiber, through a variety of vegetables and fruits to take advantage of many phytochemicals. Plant-based foods are full of antioxidants and help to decrease inflammation. In the process, it helps with feeling full and fighting hunger, healthy weight loss, as well as help improve your gut bacteria (read my post on gut health if you haven’t).



3. Disruption of circadian rhythms:

In our hypothalamus, we have a central pacemaker, or clock, that mainly acts through its powerful influence over the endocrine system, affecting many hormones including cortisol, insulin and others. We also have peripheral clocks throughout our body that are synchronized by the central clock. These clocks regulate gene expression that affects cell function.


When disruption of the circadian rhythm occurs, this circadian misalignment, in humans, can result in insulin resistance. Studies have shown sleep deprivation and dysregulation like that in night shift workers are associated with a greater risk of developing obesity, T2 diabetes, cardiovascular disease, cancers and metabolic syndrome. The circadian clocks even affect our gut microbiome, the bacteria that live in our intestines.


How does disruption of the body clock affect things?


First, some background.


At the mitochondrial level, metabolic processes have byproducts called reactive oxygen species. It is normal to have these substances present in regulated amounts, but when present in excess, lead to cell damage.


Many substances, like Vitamin C, E and glutathione play a role in neutralizing these radical oxygen byproducts.


The levels of these substances appear to vary by the time of day, leading to the inability to handle the “stress” of environmental stresses (chemical pollutants) or due to other physiological reasons (poor or inappropriate diet, late night eating, life style).


When this happens, cells enter a state called oxidative stress. Therefore, disruption of circadian rhythms can lead to cell damage by causing an imbalance in this process.


Oxidative stress is linked to aging, inflammation, obesity, development of heart disease, and cancers.


How to Build Metabolic Resilience:

  • Prioritize sleep and times for sleep & eating.
  • Work to restore a normal sleep pattern. Keep consistent bedtime and wake up time as much as possible.
  • Aim for 7-8 hours of sleep a night.
  • Avoid bright lights, blue light, computers/screens in the late evening hours. Get blue light blocking glasses or screens if needed.
  • Aim to eat during waking, daylight hours most days. That is when our mitochondria and metabolism is optimized to process food, allowing time free of eating in the evening and night for rest and repair as described above.


I hope you walk away from this 2 part series on the importance of building metabolic resilience armed with the information you need to empower you to make healthy lifestyle changes. All your action have an impact on your cells and metabolism! We cannot minimize the effects of unhealthy lifestyle stressors and how they affect cell health, our metabolism and eventually lead to development of health problems we see every day. It is my hope you that you start using some of the tools I have offered to you here right away to start building your metabolic resilience. Which ones will you start with today?


As always, please note this is not medical advice. Please discuss specific health concerns and lifestyle changes with your personal physician.

In health,

Dr M 





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