Literally "heat production", thermogenesis indicates a very interesting metabolic process. In this article, we discover what role it plays in the context of the energy balance and what are the ways to activate it and exploit its health benefits.
The energy balance
The total energy expenditure of an individual is determined by:
- Basal metabolic rate, that is the energy necessary to ensure the proper performance
of the body's vital functions.
- Physical activity , including the expenditure due to volitional physical exercise (Exercise
Actvity Thermogenesis or EAT) and that relating to activities carried out in everyday life
“involuntarily” (Non Exercise Activity Thermogenesis or NEAT).
- Adaptive thermogenesis which includes diet-induced thermogenesis, i.e. the
energy cost resulting from the absorption and metabolization of nutrients and
thermogenesis in relation to the environment.
Conditions of positive energy balance, in which the caloric intake exceeds the needs,
cause in the long term the onset of problems such as obesity. Diet and physical activity
are the main weapons for building a healthy lifestyle and monitoring body weight.
Common approaches based on calorie restriction often show limitations related to long-term sustainability when compared to lifestyle changes (increase in NEAT). However, the body undergoes continuous adaptation of a neuroendocrine nature, which can negatively affect energy expenditure, reducing it. Hence the idea of seeking alternative strategies to manage this delicate balance was born.
The thermogenesis process takes place mainly in the muscle and adipose tissue, following precise stimuli of various kinds (environmental, endocrine, pharmacological and nutritional).
Situations such as exposure to cold, for example, force the body to give energy
to the environment. To counter these losses and avoid possible compromises of
physiological functions , the body puts in place real survival mechanisms.
The muscles, they contract rapidly in involuntary way, giving rise to the thermogenesis by thrill (Shivering Thermogenesis or ST) , which involves the dissipation of energy in the form of heat without actual myofibrillar work swing.
Adipose tissue, on the other hand, is actively involved through a different mechanism known as Non-Shivering Thermogenesis (NST) .
Brown (B.A.T.) and beige adipose fabric
The NST process takes place in brown adipose tissue ( Brown Adipose Tissue or BAT), characterized by groups of adipocytes within which a considerable density of mitochondria can be found.
Discovered in mice and subsequently identified also in humans, BAT is located in areas
particularly sensitive to temperature changes where it plays a protective role. In recent times, the implications as a real player in the panorama of metabolic health have also been considered.
Recently, an additional cellular subpopulation has been identified within the
white adipose tissue deposits . These adipocytes, called beige, originate from white adipocytes following a very complex molecular process known asbrowning and also have an appreciable mitochondrial quantity.
UCP1: the protein that generates heat
Contrary to the classic white adipocytes, with an energy storage function, these two
types of adipocytes exploit the mitochondria inside them to oxidize fatty acids and glucose
rather than store them as an energy reserve. Paradoxical, yet.
The effect is mediated by a class of mitochondrial Protein known as UCPs (uncoupling Protein), in particular UCP1 or thermogenin , which allows the energy obtained from the oxidation of the substrates to be not used for the production of ATP, but transformed into heat. This phenomenon is known as decoupling of oxidative phosphorylation .
Exploit thermogenesis: why
The possibility of generating heat and burning extra calories opens the door to a new and innovative approach in dealing with situations related to excess energy. Understanding the activation mechanisms of thermogenesis currently represents one of the most fascinating challenges for the world of scientific research. Leaving aside the pharmacological approach, the literature is rich in research on nutritional compounds potentially capable of acting on several fronts of the process: activating BAT, stimulating browning or promoting the expression and activity of UCP1. Simply put, it's all about inducing non-thrilling thermogenesis and diverting excess nutrients to oxidation.
Active ingredients useful for thermogenesis
Bitter Orange (Citrus aurantium)
Bitter orange contains synephrine , an alkaloid compound structurally similar to
norepinephrine, adrenaline and especially ephedrine, able to bind to β3 adrenergic receptors facilitating the mobilization of triglycerides from adipose reserves for subsequent oxidation.
Capsaicin and other capsainoids present in chilli show a marked activity in increasing energy expenditure, activating BAT and promoting oxidation. It is hypothesized that these actions derive mainly from the beta-adrenergic signal, with stimulation of the sympathetic nervous system and release of catecholamines.
The impact of caffeine on energy expenditure is widely investigated: it increases the
metabolic rate , oxygen consumption and stimulates the release of lipid reserves for beta oxidation. Furthermore, acting as a stimulant on the sympathetic nervous system, it participates in the release of catecholamines, which can have a positive effect on BAT.
Green coffee beans contain chlorogenic acid, a polyphenol capable of increasing
BAT glucose uptake, causing it to produce heat. In addition, it appears to act on
mitochondrial function by increasing the expression of UCP1.
From the peel it is possible to obtain hydroxycitric acid, a molecule that has shown a strong action limiting the lipogenesis process through the inhibition of the citrate lyase enzyme responsible for the production of acetyl coenzyme A necessary for the synthesis of new lipid molecules.
Pomegranate contains punicalagin, a polyphenol which once metabolized by the
intestinal flora is converted to urolithin A. This molecule, already investigated in
cellular aging processes , has shown a strong ability to induce BAT and stimulate browning
through the increase levels of thyroid hormone T3, one of the main differentiation stimuli.
Laboratory studies show an action on the AMPK-Sirt1-PGC1α axis, one of the main molecular pathways that govern the physiological processes of brown adipose tissue. In light of this, it is likely that the molecule can exert some action in inducing a greater activation of the thermogenesis process in this tissue.
Essential Amino Acids
We are used to dealing with these compounds in other contexts, but the science regarding the potential of essential amino acids knows no bounds. Italian studies have highlighted the role of specific amino acid mixtures on metabolic health, highlighting an involvement in inducing mitochondrial biogenesis and activating thermogenesis in BAT, strongly limiting body weight gain and at the same time improving numerous metabolic parameters.
Overall, although mostly referred to a laboratory context, the evidence lays solid foundations for a future application of these compounds for multiple situations, from the formulation of products with effective thermogenic Energy to the actual treatment of metabolic disorders, such as obesity and diabetes.
Cohen, P., Kajimura, S. The cellular and functional complexity of thermogenic fat. Nat Rev Mol Cell Biol (2021). https://doi.org/10.1038/s41580-021-00350-0
Betz, M., Enerbäck, S. Targeting thermogenesis in brown fat and muscle to treat obesity and
metabolic disease. Nat Rev Endocrinol 14, 77–87 (2018). https://doi.org/10.1038/nrendo.2017.132
Reguero M, Gómez de Cedrón M, Wagner S, Reglero G, Quintela JC, Ramírez de Molina A. Precision Nutrition to Activate Thermogenesis as a Complementary Approach to Target Obesity and Associated-Metabolic-Disorders. Cancers (Basel). 2021;13(4):866. Published 2021 Feb 18. doi:10.3390/cancers13040866
Reguero M, Gómez de Cedrón M, Reglero G, Quintela JC, Ramírez de Molina A. Natural Extracts to Augment Energy Expenditure as a Complementary Approach to Tackle Obesity and Associated Metabolic Alterations. Biomolecules. 2021 Mar 10;11(3):412. doi: 10.3390/biom11030412. PMID:33802173; PMCID: PMC7999034.
Scarano F, Gliozzi M, Zito MC, Guarnieri L, Carresi C, Macrì R, Nucera S, Scicchitano M, Bosco F,
Ruga S, Coppoletta AR, Mollace R, Maiuolo J, Bava I, Cardamone A, Ragusa M, Palma E, Musolino V, Mollace V. Potential of Nutraceutical Supplementation in the Modulation of White and Brown Fat Tissues in Obesity-Associated Disorders: Role of Inflammatory Signalling. Int J Mol Sci. 2021 Mar 25;22(7):3351. doi: 10.3390/ijms22073351. PMID: 33805912.
Choi, Y., Yu, L. Natural Bioactive Compounds as Potential Browning Agents in White Adipose
Tissue. Pharm Res 38, 549–567 (2021). https://doi.org/10.1007/s11095-021-03027-7
Van Schaik L, Kettle C, Green R, Irving HR, Rathner JA. Effects of Caffeine on Brown Adipose Tissue Thermogenesis and Metabolic Homeostasis: A Review. Front Neurosci. 2021 Feb 4;15:621356. doi: 10.3389/fnins.2021.621356. PMID: 33613184; PMCID: PMC7889509.
Velickovic, K., Wayne, D., Leija, H.A.L. et al. Caffeine exposure induces browning features in adipose tissue in vitro and in vivo. Sci Rep 9, 9104 (2019). https://doi.org/10.1038/s41598-019-45540-1
Chlorogenic Acid Stimulates the Thermogenesis of Brown Adipocytes by Promoting the Uptake of Glucose and the Function of Mitochondria.
Xue Han Yuxin Zhang Jielong Guo Yilin You Jicheng Zhan Weidong Huang, Chlorogenic Acid
Stimulates the Thermogenesis of Brown Adipocytes by Promoting the Uptake of Glucose and the Function of Mitochondria https://doi.org/10.1111/1750-3841.14838
Jena BS, Jayaprakasha GK, Singh RP, Sakariah KK. Chemistry and biochemistry of (-)-
hydroxycitric acid from Garcinia. J Agric Food Chem. 2002 Jan 2;50(1):10-22. doi:
10.1021/jf010753k. PMID: 11754536.
Xia B, Shi XC, Xie BC, Zhu MQ, Chen Y, et al. (2020) Urolithin A exerts antiobesity effects through enhancing adipose tissue thermogenesis in mice. PLOS Biology 18(3): e3000688. https://doi.org/10.1371/journal.pbio.3000688
Chiara Ruocco, Maurizio Ragni, Fabio Rossi, Pierluigi Carullo, Veronica Ghini, Fabiana Piscitelli, Adel e Cutignano, Emiliano Manzo, Rafael Maciel Ioris, Franck Bontems, Laura Tedesco, Carolina M. Greco, Annachiara Pino, Ilenia Severi, Dianxin Liu, RyanP. Ceddia, Luisa Ponzoni, Leonardo Tenori, Lisa Rizzetto, Matthias Scholz, Kieran Tuohy, Francesco Bifari, Vincenzo Di
Marzo, Claudio Luchinat, Michele O. Carruba, Saverio Cinti, Ilaria Decimo, Gianluigi Condorelli, Roberto Coppari, Sheila Collins, Alessandra Valerio, Enzo Nisoli . Manipulation of Dietary Amino Acids Prevents and Reverses Obesity in Mice Through Multiple Mechanisms That Modulate Energy Homeostasis, Diabetes Nov 2020, 69 (11) 2324-2339; DOI: 10.2337/db20-0489