A protein known as the steroid receptor coactivator-1 (SRC-1) helps regulate body weight by controlling the function of neurons involved in eating impulses, a study reveals.
The study, “Steroid receptor coactivator-1 modulates the function of Pomc neurons and energy homeostasis,” was published in the journal Nature Communications.
The steroid receptor coactivator-1 protein is known to play a key role in the regulation of body weight, shown in a previous study where mice without SRC-1 became obese. However, the exact molecular mechanisms behind the protein’s role were unknown until now.
They found that SRC-1 is present at high levels in the hypothalamus — the brain region controlling appetite — particularly within neurons producing the pro-opiomelanocortin (POMC) peptide.
These are one of two groups of neurons controlling appetite. While neurons that express the agouti-related protein (Agrp) increase appetite, those that produce POMC promote a feeling of fullness.
“We discovered that SRC-1 is highly expressed in the hypothalamus of mice — a brain area that regulates appetite — specifically in neurons that express the Pomc gene,” Yong Xu, MD, PhD, said in a press release written by Ana Maria Rodríguez. Zu is a researcher at the Baylor College of Medicine and Texas Children’s Hospital and one of the study’s co-lead authors.
Researchers saw that SRC-1 activated the POMC gene, which provides the instructions to make the POMC protein. As a result, mice lacking the SRC-1 gene had less POMC in their neurons and eventually became obese.
They then investigated the mechanisms underlying SRC-1’s regulatory role and found that SRC-1 was needed for leptin — the major hormone controlling appetite — to exert its effect. Leptin is basically a signal that a person is full, working by activating neurons producing the POMC peptide.
Finally, since genetic variants of the SCR-1 gene are often found in obese children, the researchers explored the potential role of SRC-1 in human obesity.
Analysis showed that 14 of 15 variants found in severely obese children impaired the function of SRC-1, causing a reduction in leptin-mediated signaling. Variants in the SRC-1 gene found in healthy children had no detrimental effects.
To confirm these results, the researchers created mice carrying one of the genetic variants they had identified in the obese children. Consistent with prior findings, the animals ate more and gained more weight.
These findings explain, for the first time, the role of SRC-1 in obesity and support the potential for targeting SRC-1 as a strategy for weight loss.
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