Chaperone proteins in fat cells branded as culprits in metabolic problems

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A new study, funded by the National Institutes of Health (NIH), pinpoints protein culprits in fat cells that may make us more susceptible to metabolic problems, like insulin resistance, type 2 diabetes or fatty liver disease, as we age.
These chaperone proteins, known as adipocyte fatty acid-binding proteins (A-FABPs), are carrier proteins that bind fatty acids, transport them within cells, regulate their storage and control lipolysis, their release from storage.
A-FABPs are also capable of modulating gene expression in fat cells and may be important mediators of inflammation due to their expression in macrophages.
Previous research suggested that rendering mice A-FABP-deficient reduced their risk of developing type 2 diabetes, even if they were obese to start with or consumed a higher-fat, low-quality diet.
Silencing a specific type of A-FABPs called A-FABP4, in particular, has been shown to protect against the development of insulin resistance and aspects of the metabolic syndrome.
Human studies indicate that those who are overweight tend to have higher circulating A-FABP levels and these have been associated with metabolic syndrome during a five-year follow-up study, independently of fatness or insulin resistance.
In this new paper, Harvard T.H. Chan School of Public Health scientists genetically engineered mice to lack A-FABPs and found that they fared better against metabolic problems as they aged, compared with mice that had active FABPs in their fat tissue.
These mice gained less weight, displayed lower levels of adipose tissue inflammation, had better glucose tolerance and insulin sensitivity, and a lower incidence of fatty liver disease, than their peers.
Further, when researchers studied the A-FABP-deficient mice at a molecular level, they found alterations in tissue gene expression and variations in metabolites that were similar to the ones occuring during calorie restriction (CR).
Those beneficial effects were observed in mice that were in an age period equivalent to 35 or 40 human years and were more evident in female than in male mice. No improvement to lifespan was however seen concurrently with these positive changes, as opposed to CR.
These findings suggest that inhibiting A-FABPs could confer protection from a wide range of metabolic problems prevalent in middle age, although further research is needed to confirm this.