Inflammatory Immune Cells Make Fat Harder to Lose as Well as Worse for Health

Excess visceral fat is bad for you. One primary reason is that fat cells interact with the immune cells called macrophages to produce higher levels of chronic inflammation, and that in turn accelerates the progression of age-related dysfunction and disease. Further, as aging progresses even normal levels of fat tissue become ever worse for health, due to a variety of detrimental changes in the immune system and tissues - the accumulation of forms of molecular damage that generate further inflammation and other tissues.

The research noted here outlines yet another way in which the relationship between fat and macrophages sabotages the prospects of older individuals: it appears that one part of the damage done to the normal operation of metabolism is that the activities of inflammatory macrophages make it harder to reduce fat tissue through activity and diet. Everyone past a certain age notices that maintaining a thinner physique becomes ever more work, and here is one of the reasons as to why this is the case. As with all matters involving inflammation in fat tissue, it remains to be seen how much of this is due to the growing presence of senescent cells with age, potent sources of inflammation and tissue dysfunction as they are.

Older adults, regardless of body weight, have increased belly fat. However, when they need to expend energy, older people do not burn the energy stored in fat cells as efficiently as younger adults, leading to the accumulation of harmful belly fat. The underlying cause for this unresponsiveness in fat cells was unknown. In a new study, researchers focused on specialized immune cells known as macrophages, which are typically involved in controlling infections. They discovered a new type of macrophage that resides on the nerves in belly fat. These nerve-associated macrophages become inflamed with age and do not allow the neurotransmitters, which are chemical messengers, to properly function.

The researchers also isolated the immune cells from fat tissue of young and old mice, and then sequenced and computationally modelled the genome to understand the problem. "We discovered that the aged macrophages can break down the neurotransmitters called catecholamines, and thus do not allow fat cells to supply the fuel when demand arises." The researchers found that when they lowered a specific receptor that controls inflammation, the NLRP3 inflammasome, in aged macrophages, the catecholamines could act to induce fat breakdown, similar to that of young mice.

In further experiments, the researchers blocked an enzyme that is increased in aged macrophages, restoring normal fat metabolism in older mice. This enzyme, monoamine oxidase-A or MAOA, is inhibited by existing drugs in the treatment of depression. "Theoretically one could repurpose these MAOA inhibitor drugs to improve metabolism in aged individuals." The researchers cautioned that more research is needed to specifically target these drugs to belly fat and to test the safety of this approach. In future research, the team will further examine the immune cells and their interaction with nerves, and how this neuro-immune dialogue controls health and disease. If controlling inflammation in aging immune cells can improve metabolism, it may have other positive effects on the nervous system or on the process of aging itself.



When reading the (now seemingly) weekly articles on how rising inflammation and senescent cells harm everyone over a certain age, I always think back to the mouse models, and how a ~25% increase in lifespan versus controls was achieved.

I used to think the clearance of senescent cells in humans with drugs won't clear as many cells as effectively as the germline genetic engineering plus drug approach used in those experiments. So the effect on human lifespan/healthspan should be less than 25%.

But do mice even suffer from derangements in the metabolism of fat as they age? Is there a possibility that senescent cell removal will have a larger effect in humans than in mice?

Posted by: Jim at September 28th, 2017 6:34 AM
Comment Submission

Post a comment; thoughtful, considered opinions are valued. New comments can be edited for a few minutes following submission. Comments incorporating ad hominem attacks, advertising, and other forms of inappropriate behavior are likely to be deleted.

Note that there is a comment feed for those who like to keep up with conversations.