Obesity and its complications—including type 2 diabetes, cardiovascular disease, and certain cancers—constitute a rising global epidemic that has imposed a substantial burden on health and healthcare systems over the years. It is becoming increasingly clear that there is a link between obesity and the gut microbiota. Gut dysbiosis, characterized as microbial imbalance, has been consistently associated with obesity in both humans and animal models, and can be reversed with weight loss. Emerging evidence has shown that microbial-derived metabolites such as short-chain fatty acids (SCFAs)—including acetate, propionate, and butyrate—provide benefits to the host by impacting organs beyond the gut, including adipose tissue. In this review, we summarize what is currently known regarding the specific mechanisms that link gut-microbial-derived SCFAs with adipose tissue metabolism, such as adipogenesis, lipolysis, and inflammation. In addition, we explore indirect mechanisms by which SCFAs can modulate adipose tissue metabolism, such as via perturbation of gut hormones, as well as signaling to the brain and the liver. Understanding how the modulation of gut microbial metabolites such as SCFAs can impact adipose tissue function could lead to novel therapeutic strategies for the prevention and treatment of obesity.

Serum amyloid A (SAA) subtypes 1–3 are well-described acute phase reactants that are elevated in acute inflammatory conditions such as infection, tissue injury, and trauma, while SAA4 is constitutively expressed. SAA subtypes also have been implicated as playing roles in chronic metabolic diseases including obesity, diabetes, and cardiovascular disease, and possibly in autoimmune diseases such as systemic lupus erythematosis, rheumatoid arthritis, and inflammatory bowel disease. Distinctions between the expression kinetics of SAA in acute inflammatory responses and chronic disease states suggest the potential for differentiating SAA functions. Although circulating SAA levels can rise up to 1,000-fold during an acute inflammatory event, elevations are more modest (∼5-fold) in chronic metabolic conditions. The majority of acute-phase SAA derives from the liver, while in chronic inflammatory conditions SAA also derives from adipose tissue, the intestine, and elsewhere. In this review, roles for SAA subtypes in chronic metabolic disease states are contrasted to current knowledge about acute phase SAA. Investigations show distinct differences between SAA expression and function in human and animal models of metabolic disease, as well as sexual dimorphism of SAA subtype responses.

Obesity is a global public health issue and major risk factor for pathological conditions, including type 2 diabetes, dyslipidemia, coronary artery disease, hepatic steatosis, and certain types of cancer. These metabolic complications result from a combination of genetics and environmental influences, thus contributing to impact whole-body homeostasis. Mechanistic animal and human studies have indicated that an altered gut microbiota can mediate the development of obesity, leading to inflammation beyond the intestine. Moreover, prior research suggests an interaction between gut microbiota and peripheral organs such as adipose tissue via different signaling pathways; yet, to what degree and in exactly what ways this inter-organ crosstalk modulates obesity remains elusive. This review emphasizes the influence of circulating gut-derived short chain fatty acids (SCFAs) i.e., acetate, propionate, and butyrate, on adipose tissue metabolism in the scope of obesity, with an emphasis on adipocyte physiology in vitro and in vivo. Furthermore, we discuss some of the well-established mechanisms via which microbial SCFAs exert a role as a prominent host energy source, hence regulating overall energy balance and health. Collectively, exploring the mechanisms via which SCFAs impact adipose tissue metabolism appears to be a promising avenue to improve metabolic conditions related to obesity.