Metabolic Insights into Caffeine's Anti-Adipogenic Effects: An Exploration through Intestinal Microbiota Modulation in Obesity

Abstract

Obesity, a chronic condition marked by the excessive accumulation of adipose tissue, not only affects individual well-being but also significantly inflates healthcare costs. The physiological excess of fat manifests as triglyceride (TG) deposition within adipose tissue, with white adipose tissue (WAT) expansion via adipocyte hyperplasia being a key adipogenesis mechanism. As efforts intensify to address this global health crisis, understanding the complex interplay of contributing factors becomes critical for effective public health interventions and improved patient outcomes. In this context, gut microbiota-derived metabolites play an important role in orchestrating obesity modulation. Microbial lipopolysaccharides (LPS), secondary bile acids (BA), short-chain fatty acids (SCFAs), and trimethylamine (TMA) are the main intestinal metabolites in dyslipidemic states. Emerging evidence highlights the microbiota's substantial role in influencing host metabolism and subsequent health outcomes, presenting new avenues for therapeutic strategies, including polyphenol-based manipulations of these microbial populations. Among various agents, caffeine emerges as a potent modulator of metabolic pathways, exhibiting anti-inflammatory, antioxidant, and obesity-mitigating properties. Notably, caffeine's anti-adipogenic potential, attributed to the downregulation of key adipogenesis regulators, has been established. Recent findings further indicate that caffeine's influence on obesity may be mediated through alterations in the gut microbiota and its metabolic byproducts. Therefore, the present review summarizes the anti-adipogenic effect of caffeine in modulating obesity through the intestinal microbiota and its metabolites.

Keywords: anti-adipogenic effects; caffeine; gut microbiota; intestinal metabolites; metabolic insights; obesity.

Figure 1

Influence of the intestinal microbiota and its metabolites on organs and tissues, especially in the context of dyslipidemia. The microbiota produces bioactive components through the metabolization of dietary elements, the process of which is influenced by environmental signals and the type of diet. Gut microbiota signaling metabolites enable communication with host organs and tissues. Metabolites produced by GMOs are linked to changes in the LPL function, NAFLD, inhibition of RCT, and adipocyte dysfunction or inflammation. Adapted from [19].

Figure 2

Caffeine exerts its mechanism of action during lipolysis in adipocytes, leading to the promotion of beta-oxidation and thermogenesis. Caffeine achieves a reduction in the size of adipocyte lipid droplets and adipocyte size through various mechanisms, such as an increase in catecholamine secretion and subsequent activation of hormone-sensitive lipase (HSL), blockade of adrenergic receptors, and elevation of cAMP levels. Additionally, caffeine promotes beta-oxidation by suppressing fatty acid synthase (FAS) and upregulating peroxisome proliferator-activated receptor alpha (PPARα). It also stimulates brown adipose tissue (BAT) by increasing peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α), thereby promoting thermogenesis. Adapted from [157]. ↑ Increase.