MitObesity drugs

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MitObesity drugs

Description

Bioactive mitObesity compounds are drugs and nutraceuticals with more or less reproducible beneficial effects in the treatment of diverse preventable degenerative diseases implicated in comorbidities linked to obesity, characterized by common mechanisms of action targeting mitochondria.

Reference: BME and mitObesity

Events on mitObesity

2023 Jul 27-30: » Bioenergetics Communications on mitObesity and Healthy Aging. 15th MiPconference, Obergurgl, Austria

2023 Jun 06: » Health Innovation Summit 2023 Vienna AT

Healthy reference population

Body mass excess

BFE

BME cutoffs

BMI

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V_O₂max

mitObesity drugs

Communicated by Gnaiger Erich 2020-02-12
in: Catastrophe XXX XXX-mass Carol on BME and mitObesity of X-mass Carol

What do metformin, melatonin and other bioactive mitObesity compounds have in common?

Compromised mitochondrial fitness across metabolically active organs provides the mechanistic link between obesity and associated comorbidities — such as diabetes, hypertension and chronic hear failure, neurodegenerative diseases and several types of cancer — bound to redox imbalance, inflammation, oxidative stress and derangement of glucose/fatty acid homeostasis. Bioactive mitObesity compounds have in common that they are increasingly recognized as being effective not in only one but several preventable, non-communicable comorbidities linked to obesity. The fact that they are targeting mitochondria provides strong evidence for the role of mitochondria-linked mechanisms of action underlying the mitObesity syndrome.

Metformin has been introduced as the drug of choice for the treatment of type 2 diabetes and is particularly effective in obese patients or diabesity. Today metformin and melatonin are discussed in cancer therapy, prevention of neurodegenerative diseases and cardiac ischemia-reperfusion injury, becoming prototypes of so-called anti-aging drugs. Recognition of the mitObesity syndrome may shed new light on the mysteries of anti-aging therapies, with body mass excess, BME, and mitochondrial dysfunction implicated in vicious cause-and-effect feedback cycles.

Discussion of Artemisinin in the context of bioactive mitObesity compounds may be surprising, since it is a drug mainly known in the field of malaria — the prototype of a communicable disease, unrelated to obesity. In contrast, bioactive mitObesity compounds address non-communicable diseases associated with obesity. However, the involvement of mitochondria in the mode of action of bioactive mitObesity compounds and the anti-tumorigenic effect of artemisinin (Sun 2017 Sci Rep) provide an interesting link.

MitoPedia: mitObesity drugs

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Term	Abbreviation	Description
Aspirin		Aspirin is a widely applied drug that requires dosage adjusted to individual body mass. It is a non-selective COX inhibitor and exerts an effect on long-chain fatty acid transport into mitochondria.
Curcumin		Curcumin has been shown to possess significant anti-inflammatory, anti-oxidant, anti-carcinogenic, anti-mutagenic, anti-coagulant and anti-infective effects. The protective effects of curcumin on rat heart mitochondrial injuries induced by in vitro anoxia–reoxygenation were evaluated by Xu et al 2013. It was found that curcumin added before anoxia or immediately prior to reoxygenation exhibited remarkable protective effects against anoxia–reoxygenation induced oxidative damage to mitochondria.
Elamipretide	Bendavia	Bendavia (Elamipretide) was developed as a mitochondria-targeted drug against degenerative diseases, including cardiac ischemia-reperfusion injury. Clinical trials showed variable results. It is a cationic tetrapeptide which readily passes cell membranes, associates with cardiolipin in the mitochondrial inner membrane. Supercomplex-associated CIV activity significantly improved in response to elamipretide treatment in the failing human heart.
Flavonoids		Flavonoids are a group of bioactive polyphenols with potential antioxidant and anti-inflammatory effects, abundant in fruits and vegetables, and in some medicinal herbs. Flavonoids are synthesized in plants from phenylalanine. Dietary intake of flavonoids as nutraceuticals is discussed for targeting T2D and other degenerative diseases.
Melatonin	aMT	Melatonin (N-acetyl-5-methoxytryptamine, aMT) is a highly conserved molecule present in unicellular to vertebrate organisms. Melatonin is synthesized from tryptophan in the pinealocytes by the pineal gland and also is produced in other organs, tissues and fluids (extrapineal melatonin). Melatonin has lipophilic and hydrophilic nature which allows it to cross biological membranes. Therefore, melatonin is present in all subcellular compartments predominantly in the nucleus and mitochondria. Melatonin has pleiotropic functions with powerful antioxidant, anti-inflammatory and oncostatic effects with a wide spectrum of action particularly at the level of mitochondria. » MiPNet article
Metformin		Metformin (dimethylbiguanide) is mainly known as an important antidiabetic drug which is effective, however, in a wide spectrum of degenerative diseases. It is an inhibitor of Complex I and glycerophosphate dehydrogenase complex.
Rapamycin		Rapamycin is an inhibitor of the mammalian/mechanistic target of rapamycin, complex 1 (mTORC1). Rapamycin induces autophagy and dyscouples mitochondrial respiration. Rapamycin delays senescence in human cells, and extends lifespan in mice without detrimental effects on mitochondrial fitness in skeletal muscle.
Resveratrol		Resveratrol is a natural bioactive phenol prouced by several plants with antioxidant and anti-inflammatory effects. Dietary intake as nutraceutical is discussed for targeting mitochondria with a wide spectrum of action in degenerative diseases.
Spermidine		Spermidine is a polycationic bioactive polyamine mainly found in wheat germ, soybean and various vegetables, involved in the regulation of mitophagy, cell growth and cell death. Like other caloric restriction mimetics, spermidine is effective in cardioprotection, neuroprotection and anticancer immunosuppression by preserving mitochondrial function and control of autophagy.

Healthy reference population

Body mass excess

BFE

BME cutoffs

BMI

H

M

V_O₂max

mitObesity drugs

MitoPedia: BME and mitObesity

» Body mass excess and mitObesity | BME and mitObesity news | Summary |

Term	Abbreviation	Description
BME cutoff points	BME cutoff	Obesity is defined as a disease associated with an excess of body fat with respect to a healthy reference condition. Cutoff points for body mass excess, BME cutoff points, define the critical values for underweight (-0.1 and -0.2), overweight (0.2), and various degrees of obesity (0.4, 0.6, 0.8, and above). BME cutoffs are calibrated by crossover-points of BME with established BMI cutoffs.
Body fat excess	BFE	In the healthy reference population (HRP), there is zero body fat excess, BFE, and the fraction of excess body fat in the HRP is expressed - by definition - relative to the reference body mass, M°, at any given height. Importantly, body fat excess, BFE, and body mass excess, BME, are linearly related, which is not the case for the body mass index, BMI.
Body mass	m [kg]; M [kg·x^-1]	The body mass M is the mass (kilogram [kg]) of an individual (object) [x] and is expressed in units [kg/x]. Whereas the body weight changes as a function of gravitational force (you are weightless at zero gravity; your floating weight in water is different from your weight in air), your mass is independent of gravitational force, and it is the same in air and water.
Body mass excess	BME	The body mass excess, BME, is an index of obesity and as such BME is a lifestyle metric. The BME is a measure of the extent to which your actual body mass, M [kg/x], deviates from M° [kg/x], which is the reference body mass [kg] per individual [x] without excess body fat in the healthy reference population, HRP. A balanced BME is BME° = 0.0 with a band width of -0.1 towards underweight and +0.2 towards overweight. The BME is linearly related to the body fat excess.
Body mass index	BMI	The body mass index, BMI, is the ratio of body mass to height squared (BMI=M·H^-2), recommended by the WHO as a general indicator of underweight (BMI<18.5 kg·m^-2), overweight (BMI>25 kg·m^-2) and obesity (BMI>30 kg·m^-2). Keys et al (1972; see 2014) emphasized that 'the prime criterion must be the relative independence of the index from height'. It is exactly the dependence of the BMI on height - from children to adults, women to men, Caucasians to Asians -, which requires adjustments of BMI-cutoff points. This deficiency is resolved by the body mass excess relative to the healthy reference population.
Comorbidity		Comorbidities are common in obesogenic lifestyle-induced early aging. These are preventable, non-communicable diseases with strong associations to obesity. In many studies, cause and effect in the sequence of onset of comorbidities remain elusive. Chronic degenerative diseases are commonly obesity-induced. The search for the link between obesity and the etiology of diverse preventable diseases lead to the hypothesis, that mitochondrial dysfunction is the common mechanism, summarized in the term 'mitObesity'.
Healthy reference population	HRP	A healthy reference population, HRP, establishes the baseline for the relation between body mass and height in healthy people of zero underweight or overweight, providing a reference for evaluation of deviations towards underweight or overweight and obesity. The WHO Child Growth Standards (WHO-CGS) on height and body mass refer to healthy girls and boys from Brazil, Ghana, India, Norway, Oman and the USA. The Committee on Biological Handbooks compiled data on height and body mass of healthy males from infancy to old age (USA), published before emergence of the fast-food and soft-drink epidemic. Four allometric phases are distinguished with distinct allometric exponents. At heights above 1.26 m/x the allometric exponent is 2.9, equal in women and men, and significantly different from the exponent of 2.0 implicated in the body mass index, BMI [kg/m²].
Height of humans	h [m]; H [m·x^-1]	The height of humans, h, is given in SI units in meters [m]. Humans are countable objects, and the symbol and unit of the number of objects is N [x]. The average height of N objects is, H = h/N [m/x], where h is the heights of all N objects measured on top of each other. Therefore, the height per human has the unit [m·x^-1] (compare body mass [kg·x^-1]). Without further identifyer, H is considered as the standing height of a human, measured without shoes, hair ornaments and heavy outer garments.
Length	l [m]	Length l is an SI base quantity with SI base unit meter m. Quantities derived from length are area A [m²] and volume V [m³]. Length is an extensive quantity, increasing additively with the number of objects. The term 'height' h is used for length in cases of vertical position (see height of humans). Length of height per object, L_{U_X} [m·x^-1] is length per unit-entity U_X, in contrast to lentgth of a system, which may contain one or many entities, such as the length of a pipeline assembled from a number N_X of individual pipes. Length is a quantity linked to direct sensory, practical experience, as reflected in terms related to length: long/short (height: tall/small). Terms such as 'long/short distance' are then used by analogy in the context of the more abstract quantity time (long/short duration).
MitObesity drugs		Bioactive mitObesity compounds are drugs and nutraceuticals with more or less reproducible beneficial effects in the treatment of diverse preventable degenerative diseases implicated in comorbidities linked to obesity, characterized by common mechanisms of action targeting mitochondria.
Obesity		Obesity is a disease resulting from excessive accumulation of body fat. In common obesity (non-syndromic obesity) excessive body fat is due to an obesogenic lifestyle with lack of physical exercise ('couch') and caloric surplus of food consumption ('potato'), causing several comorbidities which are characterized as preventable non-communicable diseases. Persistent body fat excess associated with deficits of physical activity induces a weight-lifting effect on increasing muscle mass with decreasing mitochondrial capacity. Body fat excess, therefore, correlates with body mass excess up to a critical stage of obesogenic lifestyle-induced sarcopenia, when loss of muscle mass results in further deterioration of physical performance particularly at older age.
VO2max	V_O₂max; V_O₂max/M	Maximum oxygen consumption, V_O₂max, is and index of cardiorespiratory fitness, measured by spiroergometry on human and animal organisms capable of controlled physical exercise performance on a treadmill or cycle ergometer. V_O₂max is the maximum respiration of an organism, expressed as the volume of O₂ at STPD consumed per unit of time per individual object [mL.min^-1.x^-1]. If normalized per body mass of the individual object, M [kg.x^-1], mass specific maximum oxygen consumption, V_O₂max/M, is expressed in units [mL.min^-1.kg^-1].

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