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June 7, 2016

Copper May Be Fat-Burning Gold

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    A fluorescent probe creates a heat map of copper in white fat cells. Higher levels of copper are shown in yellow and red. The left panel shows normal levels of copper from fat cells of control mice and the right panel shows cells deficient in copper. [Lakshmi Krishnamoorthy and Joseph Cotruvo, Jr./UC Berkeley]

    A freshly minted study indicates that copper could help restore a natural way to burn fat. Copper, it turns out, can alter the balance of metabolic accounts through its influence on a biochemical signaling pathway.

    That copper is connected to fat metabolism isn’t an altogether surprising finding. Copper levels in animal feed have been associated with the fattiness of meat. Yet this observation, from the field of animal husbandry, lacked the support of biochemical studies.

    Eager to correct this deficit, scientists at Lawrence Berkeley National Laboratory and the University of California are putting in their two cents. On the basis of animal studies and cell culture analyses, these scientists maintain that copper is “an endogenous regulator of lipolysis, the breakdown of fat, which is an essential process in maintaining body weight and energy stores.”

    The scientists, who were led by the Berkeley Lab’s Christopher J. Chang, Ph.D., published a study that appeared June 6 in the journal Nature Chemical Biology. The study, “Copper Regulates Cyclic-AMP-Dependent Lipolysis,” underscores the growing appreciation of copper as an essential nutrient for human physiology.

    “Using a mouse model of genetic copper misregulation, in combination with pharmacological alterations in copper status and imaging studies in a 3T3-L1 white adipocyte model, we found that copper regulates lipolysis at the level of the second messenger, cyclic AMP (cAMP), by altering the activity of the cAMP-degrading phosphodiesterase PDE3B,” wrote the article’s authors. “Biochemical studies of the copper-PDE3B interaction establish copper-dependent inhibition of enzyme activity and identify a key conserved cysteine residue in a PDE3-specific loop that is essential for the observed copper-dependent lipolytic phenotype.”

    To establish a copper–fat link, the scientists used mice with a genetic mutation that causes the accumulation of copper in the liver. Notably, these mice have larger than average deposits of fat compared with normal mice. The altered mice essentially model a human condition known as Wilson's disease, which is potentially fatal if left untreated.

    Analysis of the altered mice revealed that the abnormal buildup of copper was accompanied by lower than normal lipid levels in the liver compared with control groups of mice. The researchers also found that the white adipose tissue, or white fat, of the altered mice had lower levels of copper compared with the control mice and correspondingly higher levels of fat deposits.

    They then treated the altered mice with isoproterenol, a beta agonist known to induce lipolysis, the breakdown of fat into fatty acids, through the cyclic adenosine monophosphate (cAMP) signaling pathway. They noted that the altered mice exhibited less fat-breakdown activity compared with control mice.

    The results prompted the researchers to conduct cell culture analyses to clarify the mechanism by which copper influences lipolysis. The researchers used inductively coupled plasma mass spectroscopy (ICP-MS) equipment at Berkeley Lab to measure levels of copper in fat tissue. They found that copper binds to phosphodiesterase 3, or PDE3, an enzyme that binds to cAMP, halting cAMP’s ability to facilitate the breakdown of fat.

    "When copper binds phosphodiesterase, it's like a brake on a brake," said Dr. Chang. "That's why copper has a positive correlation with lipolysis."

    "We find that copper is essential for breaking down fat cells so that they can be used for energy," elaborated Dr. Chang. "The more copper there is, the more the fat is broken down. We think it would be worthwhile to study whether a deficiency in this nutrient could be linked to obesity and obesity-related diseases."

    Dr. Chang, however, cautions against ingesting copper supplements as a result of the current study’s results. Too much copper can lead to imbalances with other essential minerals, including zinc.

    Nonetheless, according to the Food and Nutrition Board of the Institute of Medicine, an adult's estimated average dietary requirement for copper is about 700 micrograms per day. The Food and Nutrition Board also found that only 25% of the U.S. population gets enough copper daily.

    "Copper is not something the body can make, so we need to get it through our diet," added Dr. Chang. "The typical American diet, however, doesn't include many green leafy vegetables. Asian diets, for example, have more foods rich in copper."

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