Macrophage regulation of adipocyte biology
During the progression from the lean to the obese state, adipose tissue undergoes hyperplasia as well as hypertrophy in an attempt to cope with the increased demand for triglyceride storage. This requires a high degree of plasticity at both the cellular and at the tissue level. Even though adipose tissue as a whole seems to be a relatively static tissue containing many adipocytes that turn over relatively slowly, these cells are embedded in an environment that can rapidly adapt to the needs of expanding and newly differentiating adipocytes.
Subclinical inflammation is frequently associated with obesity. We want to better define the acute inflammatory response during fasting. Representatives of immune-related proteins in circulation and in tissues were analyzed as potential markers for adipose tissue inflammation and modulation of the immune system. Lipopolysaccharide treatment or high fat diet leads to an increase in circulating serum amyloid (SAA) and α1-acid glycoprotein (AGP), while adipsin levels are reduced. Mouse models that are protected against diet-induced challenges, such as adiponectin overexpressing animals or mice treated with PPARgamma agonists, displayed lower SAA levels and higher adipsin levels. An oral lipid gavage increased circulating SAA concurrent with the elevation of FFA levels. Moreover, prolonged fasting increased circulating SAA and was associated with an increased number of Mac2 positive, crown-like structures and an increase in the capillary permeability in adipose tissue. This fasting-induced inflammatory response in adipose tissue was associated with increased VEGF expression and an increase in several M2-type macrophage markers. This fasting-induced switch to M2 type macrophages is impaired in metabolically challenged animals. Therefore, one of the underlying reasons for the metabolic inflexibility observed under those conditions is the prevailing lack of immunological fitness of adipose tissue.
Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
Funding: This work was supported, however funding details are unavailable.