Aging Fat

In this study Scientists want to know whether our aging fat cells are important to the onset and progression of Alzheimer’s. They have evidence that as we age, our fat becomes less efficient at producing a hormone that helps support the growth and survival of neurons and helps regulate their activity. The result can be neurons in areas of the brain important to learning and memory become dysfunctional, degenerate and we develop Alzheimer’s.

The hormone is adiponectin, which is made by fat cells, circulates in our blood and enters our brain. Inside fat cells, its production is regulate by peroxisome proliferator-activate receptor gamma, or PPAR-γ, a transcription factor that’s essential for early stage fat cells to become mature, fully functioning ones.

Team to further explore

However, investigators studying the agonists’ potential in Alzheimer’s have report difficulty; so with the drugs reaching the brain; also that the high doses need to compensate for that result; hence in side effects like edema, heart failure, liver abnormalities and weight gain. These findings have some calling for more selective PPAR-γ therapies.

In the search for a better solution, the grant is enabling Lu and her team to further explore the relationship between adiponectin made by fat cells and the cognitive decline that comes with aging. They also are looking at the receptors for adiponectin on neurons; hence in centers of learning and memory in the brain to explore their distinct function; so what happens to them with the onset and progression of Alzheimer’s and the vulnerability of the neurons with the receptors to degeneration.

Lu’s team thinks the benefit of PPAR-γ agonists in Alzheimer’s results from activating the PPAR-γ in fat cells; which increases adiponectin production, so they are using mice missing PPAR-γ in adult fat cells to look at its effects on cognition, metabolic function, the overall health of neurons and the hallmark neuro pathological lesions in a mouse model of Alzheimer’s.

Brains function better

In the brain, adiponectin has two distinct receptors on neurons, AdipoR1 and AdipoR2. Lu’s lab has find that activating adiponectin receptor 1 and disrupting adiponectin receptor 2 increases the excitability of neurons in the hippocampus while disrupting receptor 1 and activating receptor 2 decreases it.

Adiponectin has a protective, or neurotrophic, effect on neurons helping; which enable their survival, growth, repair and even regrowth. They can help neurons and their connections stay nimble, or plastic; so our brains function better, and they can continue to properly respond to our environment; also maintain other brain basics like making memories.

Genetic variations in PPAR-γ and adiponectin as well as low blood levels; so of adiponectin already are associate with an increase Alzheimer’s risk. In fact, low adiponectin levels in the cerebrospinal fluid in the brain have associate with increase production of the hallmark plaque and shrinking of the hippocampus associate with Alzheimer’s.

Alzheimer’s is the sixth leading cause of death in the United States; so according to the Centers for Disease Control and Prevention. First symptoms may appear after age 60; so the number of people with it doubles every five years beyond age 65, according to the CDC. It’s know that metabolic disorders, like obesity, cardiovascular disease and diabetes; so increase Alzheimer’s risk. In fact, Alzheimer’s is sometimes refer to as type 3 diabetes; which is thought to result from resistance to insulin in the brain.