Effects of nutrition and aging on energy metabolism and brown adipose tissue

Contact persons: Prof. Dr. Tim Schulz, Dr. Sabrina Gohlke
Team: Dr. Sabrina Gohlke, Antje Kretschmer, Georgia Lenihan-Geels, Carola Mancini
Funding: DZD-BMBF, DFG

Fig. 1: Age-related impairment of brown adipogenesis. (a) UCP1 mRNA levels in brown adipose tissue isolated from mice of different ages, e.g. young (2.5 month), middle-aged (15 months) and old (25 months). (b) UCP1 mRNA levels in subcutaneous white adipose tissue from the same age groups before and after 8 days of cold exposure. (c) UCP1 protein levels in brown adipose tissue from young (2.5 months) and middle-aged (15 months) mice. (d) UCP1 protein levels in subcutaneous white adipose tissue from the same age groups before and after 8 days of cold exposure.

Aging leads to a reduced formation and function of brown adipocytes (Fig. 1). There are two types of brown adipose tissue in the body: one that is formed directly from stem cells and one that is created under the influence of a suitable signal by directly converting mature white into brown adipocytes. The most common trigger for the formation of brown adipocytes is cold exposure. However, recent studies show that nutrition and a number of signaling molecules circulating in the blood stream can also promote the formation of brown adipocytes.

Brown fat is involved in the regulation of temperature balance and, according new findings, also influences the regulation of macronutrient metabolism. Recent studies show that brown adipose tissue does not only exist in newborns and infants, but also in adult humans. Accordingly, a loss of brown adipose tissue is associated with disorders in energy metabolism and ultimately with the development of the metabolic syndrome.

In a recently published article, we showed that the BMP (Bone Morphogenetic Protein) signaling pathway plays an important role because it influences inflammatory processes in adipose tissue. In this study, we were able to demonstrate a direct connection between the activation of BMP signaling and the development of age-related insulin resistance (Schulz et al, Diabetologia 2016).

We are currently investigating the extent to which aging processes influence the composition of adipose tissue. We pay particular attention to the function of stem cells and their microenvironment, the so-called stem cell niche. Aging leads to the depletion of specialized stem cells, which can form brown adipocytes, while the stem cells to form the much more common white adipocytes remain unaffected. Our analyzes also show that age-related changes of lipid metabolism play an important role in these processes. Aged brown adipocytes are less efficient in breaking down lipids, and intermediate products of lipid metabolism are increasingly accumulating in brown adipose tissue, which in turn inhibit the metabolic function of brown adipocytes (Gohlke et al, Mol Metab 2019; Graja et al, Aging Cell 2018).