![New insights on obesity: Burning the midnight oil and other neurological factors could be contributing to weight gain](https://www.europeanscientist.com/wp-content/uploads/thumbs/obesity-38qj3k9kcobqjlb45yomww.jpg)
Two separate studies published this week have shed some light onto why some people seem to have more trouble losing weight than others. One study published on 22 August in Science Translational Medicine has provided some insights into how the body reacts to its own fat stores and the set of molecular events that are set into motion an may impede the normal metabolic processes that suppress hunger (1). Another study published the same day in Science Advances suggests that losing just a single night of sleep can alter gene expression and impair metabolism in humans, thereby affecting body composition (2).
A hormone called leptin that is produced by adipose (fat) cells is already known to be involved in regulating food intake by communicating with a region in the brain region called the hypothalamus. Once energy stores are full, the molecule is released to suppress hunger cravings. In one of these new studies, an international team of researchers showed increased matrix metalloproteinase 2 (MMP-2) activity — an enzyme that cuts off a portion of the leptin receptor in the hypothalamus, thereby impairing its appetite-suppressing ability — in obese mice.
Use of a gene-silencing technique to disable MMP-2 reduced weight gain in mice and prevented leptin receptor cleavage, whereas viral delivery of MMP-2 to the hypothalamus promoted weight gain. Moreover, the researchers also found that treating in vitro cultures of hypothalamic cells with inflammatory compounds increased their expression of the MMP-2 gene, alluding to the potential role of inflammation in obesity. According to previous research, high-fat, high-calorie diets can induce chronic low-grade inflammation of the hypothalamus, which can increase MMP-2 production over time (3). However, these new findings may open the door to possible therapies aimed at damping down inflammation in the brain, decreasing MMP-2 activity and boosting the brain’s responsiveness to leptin.
According to a second study, researchers from Uppsala University found that sleep loss results in tissue-specific changes in DNA methylation — one of the mechanisms that regulate gene expression. This type of epigenetic modification is involved in regulating how the genes of each cell in the body are turned on or off, and is influenced by both hereditary and environmental factors.
The study looked at 15 healthy normal-weight individuals over two sessions. In randomised order, the participants were either allowed to have a normal night of sleep (eight hours) or instead kept awake the entire night, and the sleep pattern was swapped in the second session. The morning after both sessions, biopsies were taken from subcutaneous fat and skeletal muscle, as well as blood samples. The samples were then tested for metabolites including sugar molecules and different fatty and amino acids, as well as tissue-specific change in DNA methylation.
The altered DNA methylation was only seen in adipose (fat) tissue and in relation to genes that are known to be modified at the DNA methylation level in metabolic conditions such as obesity and type 2 diabetes. This may explain why shift work and chronic sleep deprivation can impair our metabolism and adversely affects body composition.
Obesity, which is closely linked to type 2 diabetes and related metabolic disorders, is increasingly more common but can be extremely challenging to treat. These findings offer new insights into understanding some of the molecular mechanisms at work and may offer the potential for developing new treatments or prevention strategies.
(1) Mazor, R. et al. Cleavage of the leptin receptor by matrix metalloproteinase–2 promotes leptin resistance and obesity in mice. Science Translational Medicine (2018). DOI: 10.1126/scitranslmed.aah6324
(2) Cedernaes, J. et al. Acute sleep loss results in tissue-specific alterations in genome-wide DNA methylation state and metabolic fuel utilization in humans. Science Advances (2018). DOI: 10.1126/sciadv.aar8590
(3) Cai, D. and Liu, T. Hypothalamic inflammation: a double-edged sword to nutritional
Diseases. Annals of the New York Academy of Sciences (2011). DOI: 10.1111/j.1749-6632.2011.06388.x