Obesity is the most prevalent, costly and harmful epidemic of the 21st
century. Considered a disease of excess, it is now known that it doesn’t take just to
have increased food intake with reduced expenditure, but a number of other factors
have increasingly been reported to have similar influence. At the center of all metabolic
pathways lie mitochondria. The powerhouses of the cell is the cornerstone of cuttingedge
research on metabolic alterations in obesity and related conditions. Boosting
mitochondrial activity, removing damaged units and producing new, energy-consuming
mitochondria are some of the strategies currently used in the development to combat
obesity. In this chapter, we will focus on the near-future applicability of therapeutic
strategies that achieve this goal. Specifically, we will address how sirtuin-activating
compounds and bile acids promote mitochondrial homeostasis in spite of constant fat
and carbohydrate insult, resulting in the unclogging of metabolic pathways and
promoting the restoration of a normal energetic, redox and functional cellular
environment. Activation of sirtuins 1 and 3 stimulates mitochondrial oxidative
metabolism and prevents the accumulation of reduced substrates, a major factor driving
cellular dysfunction in the setting of obesity. By acting on adipose tissue and
stimulating energy expenditure, which may be associated with an increase in fatty acid
oxidation, bile acids improve metabolic status.
Keywords: Adipose tissue, Bile acids, Biogenesis, Caloric restriction,
Chenodeoxycholic acid, Energy expenditure, Metabolism, Mitochondria,
Mitochondrial dysfunction, Mitophagy, Obesity, Sirtuins, Therapeutic strategies,
FXR, OXPHOS, PGC-1α, SIRT1, SIRT3, TGR5.