Fat stores have been an important survival mechanism during the evolution of humanity when food was scarce, and the timing of nutritional intake was uncertain. However, fast forward to current times when the recent explosion of chronic "overnutrition" and overeating has led to the epidemic of cardiometabolic diseases, including diabetes.

New research published in the journal Cell on February 3, 2022, reveals assertions by researchers that excess fat alone is not the real problem, but it is more the decline in the ability of the adipose fat to be flexible and able to respond to changes that occur in the body.

Lead author Claudio J. Villanueva, PhD, from the College of Life Sciences/David Geffen School of Medicine and Patrick Seale from Perelman School of Medicine at the University of Pennsylvania, and colleagues set out to explore the role of fat—beyond what is understood on the basic level as an energy storage reservoir.

Obesity is known to cause cardiometabolic diseases, including diabetes, and—in the past—that association has been based merely on excess fat; however, research is now showing that adipose tissue influences vital body function including body temperature regulation and immunologic processes. Because insulin sensitivity is also regulated by the presence of fat, the modulation of fat is seen as a future target of treatment for metabolic disease control and prevention. Since obesity has also been implicated in an increased risk of other diseases, such as cancer and in the worsening of outcomes of other diseases, the importance of this work increases—especially considering the increased mortality the medical community is seeing in obese patients during the COVID-19 pandemic.

The authors wrote, "The central role of adipose tissue dysfunction in disease and the incredible plasticity of fat tissue supports the promise of modulating fat tissue phenotypes for therapeutic purposes." They elaborated further, "Many questions and opportunities for future discovery remain, which will yield new insights into adipose tissue biology and hopefully lead to improved therapies for human disease."

The researchers highlight the importance of their work by reporting that because healthy adipose tissue is extraordinarily flexible (possesses characteristics of plasticity), it can maintain energy expenditures despite significant changes in supply and demand of nutrients available. Also, this flexibility promotes long-term energy balance, responding to cold by engaging in the production of heat, and regulating processes such as wound healing and lactation.

Excess adipose tissue precipitates a decline of this flexibility and is subsequently involved in the development of inflammation, fibrosis, catecholamine resistance, and cellular senescence. This supports the therapeutic approach of agents such as the thiazolidinediones (TZDs), which promote healthy adipose tissue expansion and enhance insulin sensitivity. The recognized success of the TZDs paves the way of the therapeutic promise of fat tissue modulation and improvement of metabolic disease and insulin resistance.

The authors concluded that there is an "urgent need to develop new therapies to combat the expanding dual epidemics of obesity and cardiometabolic disease" as the rapidly growing health crisis is reversing many of the recent gains in life expectancy and increasing strain on healthcare systems.

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