Tuesday, November 17, 2015

Microbiota connects type II immune system to lean body metabolism

There is a renewed interest in gut microbiota research. Initially, this revival of microbiota studies came from observations that obese and lean people have different gut microbiota. It is not clear how exactly microbiota modulates energy metabolism and the research is ongoing in this direction.

For example, journal Nature Medicine has just published another paper where the authors showed that microbiota modulates energy metabolism through its action on a specialized adipose tissue called brown [beige] adipose tissue.

A peculiar aspect of this study [and main reason why it was published in this journal in the first place] has to do with sophisticated methodologies the authors used to study energy metabolism in mice (such as glucose uptake assays with 2-[14C]-deoxyglucose, [18F]fluorodeoxyglucose, 2-[1-3H]deoxyglucose, micro-PET-CT, etc).

Basically, the authors showed that when mice are treated with broad spectrum antibiotics, inguinal subcutaneous and perigonadal visceral adipocytes undergo modification (browning and cell size reduction) resembling adipose tissue in Germ-free mice.

Antibiotic treatment led to the increase in Ucp-1cells in inguinal adipose tissue confirming "browning" of adipose tissue.



In addition, the authors observed "browning" of inguinal and perigonadal adipose tissues in antibiotic treated mice even at thermoneutral conditions (at 30℃ for mice).


Next, the authors showed that microbiota depletion improved "lean body" metabolism both in obese-prone [ob/ob] and high-fat diet fed [HFD] mice.


Finally, the authors showed that antibiotic treatment was associated with type II cytokine profile in "browning" inguinal adipose tissue, including presence of tyrosine hydroxylase (TH) expressing M2 MΦ.


In summary, these results [re]confirmed that microbiota played an important role in "lean body" metabolism associated with development of "brown" adipose tissue. Interestingly, two pathways known for brown adipose tissue development [exposure to low temperature and microbiota depletion] required type II immune system. Type II immune system is mostly known for its involvement in allergy and more recently tyrosine hydroxylase (TH) expressing M2 MΦ has been implicated in neuro-inflammation. It remains to be discovered whether "lean body" metabolism and allergy are interconnected or whether they represent two independent outcome of type II immunity 😕

David Usharauli

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