Fat cells found to play a central role in cognitive decline and neurodegeneration

So you've described a problem but did nothing to suggest how to reduce these fat cells. Useless.

Fat cells found to play a central role in cognitive decline and neurodegeneration

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Marshall University Joan C. Edwards School of Medicine

Summary:

New findings show that fat cells control the systemic response to brain function, causing impairment in memory and cognition in mice. The activation of Na,K-ATPase oxidant amplification loop affects the expression of important protein markers in fat cells as well as in the hippocampus, which can worsen brain function and lead to neurodegeneration.

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Findings published this week reveal new insights into the role of fat cells in cognitive decline and neurodegeneration, according to a study that involves the oxidant amplification loop led by Marshall University scientists.

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The research, published in iScience, shows that fat cells control the systemic response to brain function, causing impairment in memory and cognition in mice. The activation of Na,K-ATPase oxidant amplification loop affects the expression of important protein markers in fat cells as well as in the hippocampus, which can worsen brain function and lead to neurodegeneration. Targeting the fat cells to antagonize Na,K-ATPase may improve these outcomes.

"We have aimed to demonstrate that Na,K-ATPase signaling, specifically in adipocytes, play a central role in inducing alterations in specific regions of the brain, most notably in the hippocampus, which is critical to memory and cognitive function," said senior author Joseph I Shapiro, M.D., professor and dean of the Marshall University Joan C. Edwards School of Medicine.

Researchers used a genetically-modified mouse model that released the peptide NaKtide specifically in adipocytes, or fat cells, to find that NaKtide inhibited the signaling function of Na,K-ATPase. The adipocyte-specific NaKtide expression improved the altered phenotype of adipocytes and improved function of the hippocampus, the part of the brain associated with memory and cognition. Inducing oxidative stress through western diet increased production of inflammatory cytokines confined to adipocytes as well as altered protein markers of memory and cognition in the hippocampus.

"Western diet induces oxidant stress and adipocyte alteration through Na,K-ATPase signaling which causes systemic inflammation and affects behavioral and brain biochemical changes," said Komal Sodhi, M.D., first author and associate professor of surgery and biomedical sciences at the Joan C. Edwards School of Medicine. "Our study showed that adipocyte-specific NaKtide expression in our murine model ameliorated these changes and improved neurodegenerative phenotype."

This work builds on the groundbreaking work of the late Zijian Xie, Ph.D., who served as director of the Marshall Institute for Interdisciplinary Research from 2013 to 2020. Continued research will help determine if these findings can be confirmed in humans, representing a novel and successful therapeutic target in neurodegenerative disorders. In addition to Shapiro and Sodhi, authors of the paper included Rebecca Pratt, Xiaoliang Wang, Hari Vishal Lakhani, Sneha S. Pillai, Mishghan Zehra, Jiayan Wang, Lawrence Grover, Brandon Henderson, James Denvir, Jiang Liu, Sandrine Pierre and Thomas Nelson, all of Marshall University.

This research was supported by the National Institutes of Health Grants 1R15HL150721 (to K.S.), NIH Bench-to-Bedside award made possible by the Office of Research on Women's Health (ORWH) 736214 (to K.S. and J.I.S.), and by the BrickStreet Foundation (to J.I.S.) and by the Huntington Foundation, Inc. (J.I.S.). The GABC is supported by WV-INBRE (NIH/NIGMS P20GM103434), the COBRE ACCORD (1P20GM121299), and the WV-CTSI (2U54GM104942).

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Materials provided by Marshall University Joan C. Edwards School of Medicine. Note: Content may be edited for style and length.

Circadian Clocks Play a Key Role in Fat Cell Growth

My doctor obviously knew nothing about weight gain post stroke. He didn't reference body metabolism slowing down after age 50 and limited exercise ability which I used to do to excess allowing me to eat as I wanted. This incompetence led me to a 30 lb. weight gain which I'm still working to conquer.  

How to Increase Metabolism After 50 - WebMD

The latest here:

Circadian Clocks Play a Key Role in Fat Cell Growth

Summary: Circadian rhythm disruption plays a critical role in weight gain, a new study reports.

Source: Weill Cornell Medicine

Disruption of the circadian clocks that keep the body and its cells entrained to the 24-hour day-night cycle plays a critical role in weight gain, according to a pair of studies by Weill Cornell Medicine investigators.  

One study, published June 27, in Cell Reports revealed that stress caused by chronically administering glucocorticoid stress hormones and disturbing the normal daily cycle of release triggers a temporary protective mechanism in mice.

This mechanism boosts fat cell growth and insulin production while reducing excess blood sugar and fat levels in the bloodstream and liver.

The second study, published Aug. 8 in the Proceedings of the National Academies of Sciences, shows that fat cell precursors commit to becoming fat cells during the rest period of mice.

The studies suggest that stress and other factors that throw the body’s “clocks” out of rhythm may contribute to weight gain and suggest new treatment approaches for obesity. 

“A lot of forces are working against a healthy metabolism when we are out of circadian rhythm,” explained the senior author of both studies Dr. Mary Teruel, associate professor of biochemistry and a member of the Gale and Ira Drukier Institute for Children’s Health at Weill Cornell Medicine. “The more we understand, the more likely we will be able to do something about it.” 

 In the first study, Dr. Teruel and colleagues mimicked the disruptive effects conditions like Cushing’s disease or chronic stress have on the usual daily fluctuations in glucocorticoids, a class of stress-linked hormones.

To do this, they implanted pellets that released glucocorticoids at a constant rate over 21 days under the skin of mice and compared them with normal mice who have normal daily fluctuations. The amount of brown and white fat in the mice with the glucocorticoid pellets doubled within 21 days, and insulin levels in their bodies skyrocketed even though the mice still ate the same healthy diet as the normal mice.  

“If you stress the animals at the wrong time, it has a dramatic effect,” Dr. Teruel said. “The mice aren’t eating differently, but a big shift in metabolism causes weight gain.” 

Surprisingly, these metabolic disruptions seemed to have a “protective effect” by keeping blood sugar levels low and preventing fat from accumulating in the blood or liver. When they removed the pellets, the metabolic changes quickly reversed. 

“It shows the animals can cope with chronic stress for a while,” she said. 

In the second study, Dr. Teruel and her colleagues attached a red fluorescent protein to protein that controls the expression of important circadian clock genes and a yellow fluorescent protein to peroxisome proliferator activated receptor gamma (PPARG), a protein that regulates fat cell production. They used these two fluorescent markers to monitor the daily fluctuations of PPARG and circadian gene expression in mouse fat cell precursors.

During the rest period of the day, they found a circadian protein called CCAAT enhancer binding protein alpha (CEBPA) causes a rapid increase in the production of PPARG. Once PPARG levels reach a certain threshold, the precursor cells commit to becoming fat cells, a process that takes a few days to complete. 

“The decision to become a fat cell happens rapidly over 4 hours. It is like a switch,” she said. “It only happens at a certain time of day.”

When they removed the pellets, the metabolic changes quickly reversed. Credit: Weill Cornell Medicine

Dr. Teruel and her colleagues are now working to understand why disturbing the daily rhythms of glucocorticoids triggers temporary protective metabolic changes. They also want to learn whether prolonged stress or a high-fat diet makes these changes permanent. The results of these studies could help determine how long it is safe to treat individuals with glucocorticoid drugs for conditions like asthma. 

The research might also lead to the development of drugs that help reset circadian rhythms in people with obesity as an alternative to more invasive treatments like bariatric surgery. Another possibility might be therapies targeting the 4-hour window when fat cell precursors commit to becoming fat cells to prevent excess fat accumulation. 

Dr. Teruel and her colleagues also believe learning how to synchronize the body’s cellular and master circadian clocks will be essential.

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“Every cell in our body has an intrinsic cell clock, just like the fat cells, and we have a master clock in our brain, which controls hormone secretion,” she said. “We are trying to understand how they work together and how we can coordinate them.”  

About this circadian rhythm and weight research news

Author: Press Office
Source: Weill Cornell Medicine
Contact: Press Office – Weill Cornell Medicine
Image: The image is credited to Weill Cornell Medicine

Fat Cells Converted Into Stem Cells Can Repair Any Damaged Tissues

Personally I still think handing your doctor a pee cup and asking for stem cells is much better, but to each her own.  Or course stem cells are probably decades off before becoming useful in stroke.

Turning urine into brain cells could help fight Alzheimer’s, Parkinson’s and it is only 5 years old, plenty of time for your doctor to contact researchers and get something done. But I bet absolutely NOTHING was done by your doctor, incompetence in action once again.

Fat Cells Converted Into Stem Cells Can Repair Any Damaged Tissues

Stem cell therapies capable of regenerating any human tissue damaged by injury, disease or ageing could be available within a few years, following landmark research led by UNSW Australia researchers. Watch the video below for more details.

The repair system, similar to the method used by salamanders to regenerate limbs, could be used to repair everything from spinal discs to bone fractures, and has the potential to transform current treatment approaches to regenerative medicine. The findings were published in the Proceedings of the National Academy of Sciences journal.

“This technique is a significant advance on many of the current unproven stem cell therapies, which have shown little or no objective evidence they contribute directly to new tissue formation,” study lead author, haematologist and UNSW Associate Professor John Pimanda said.
The technique developed by UNSW researchers involves extracting adult human fat cells and treating them with the compound 5-Azacytidine (AZA), along with platelet-derived growth factor-AB (PDGF-AB) for approximately two days. The cells are then treated with the growth factor alone for a further two-three weeks.
AZA is known to induce cell plasticity, which is crucial for reprogramming cells. The AZA compound relaxes the hard-wiring of the cell, which is expanded by the growth factor, transforming the bone and fat cells into iMS cells. When the stem cells are inserted into the damaged tissue site, they multiply, promoting growth and healing.
The technique is similar to salamander limb regeneration, which is also dependent on the plasticity of differentiated cells, which can repair multiple tissue types, depending on which body part needs replacing.
Along with confirming that human adult fat cells reprogrammed into iMS stem cells can safely repair damaged tissue in mice, the researchers said further work is required to establish whether iMS cells remain dormant at the sites of transplantation and retain their capacity to proliferate on demand.
“We are currently assessing whether adult human fat cells reprogrammed into iMS cells can safely repair damaged tissue in mice, with human trials expected to begin in late 2017.” Associate Professor Pimanda said.