AsianScientist (May 15, 2013) – Scientists have identified an important regulator of energy metabolism and body weight, which could be a potential target for the treatment of obesity-related diseases.
Obesity is an increasingly pressing problem worldwide, caused by rising incomes, eating too much and not exercising enough. The hypothalamus, a region at the base of the brain, is known to play a key role in regulating appetite by sensing metabolic signals from fatty tissue and from the gastrointestinal tract.
Leptin is an appetite-suppressing hormone secreted by fat cells that acts on the neurons of the hypothalamus. Earlier studies in mice pinpointed the role of specialised proteins, known as apolipoproteins, in regulating cell signalling pathways important for appetite control, such as the leptin signalling pathway. In obese mice, the brain stops responding to leptin signalling and development of leptin resistance is thought to be a key pathogenic mechanism for overeating.
A team of Korean researchers led by Dr. Min-Seon Kim from the University of Ulsan in Seoul have now identified an apolipoprotein called clusterin that is highly expressed in the hypothalamus, and whose expression increases after food intake and in response to leptin administration. Importantly, in obese mice that were fed a high-fat diet, these changes are blunted.
Publishing in the journal Nature Communications, the scientists report that when clusterin was injected in the hypothalamus of mice, they ate less and lost weight. Conversely, when clusterin was inhibited, the mice ate more and gained weight. Notably, clusterin supplement in obese mice successfully decreased food intake and body weight.
The authors also found other key components that are crucial for clusterin-leptin signalling. While these studies have been carried out in mice, Dr. Kim hopes that these findings will lead to novel clinical therapeutic approaches for individuals where current strategies to control obesity are unsuccessful.
Dr. Kim says, “Clusterin may be a potential therapeutic target for leptin resistance and hyperphagia [overeating] when we can efficiently deliver clusterin into the brain.”
The article can be found at: Gil SY et al. (2013) Clusterin and LRP2 are critical components of the hypothalamic feeding regulatory pathway.
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Source: Nature Communications.
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