Specific Mutation Hinders Healthier Response to Weight Loss Diets, Study Suggests

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by Margarida Azevedo |

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A specific variant in the MTNR1B gene influenced the response of obese patients to two low-calorie diets, a recent study found.

People without this mutation, known as rs10830963 G allele, showed greater improvements in several measures of health, including insulin levels, low-density lipoprotein (LDL, the “bad” cholesterol), and weight loss than did those with this G allele variant.

The study, “A circadian rhythm-related MTNR1B genetic variant (rs10830963) modulate body weight change and insulin resistance after 9 months of a high protein/low carbohydrate vs a standard hypocaloric diet,” was published in the Journal of Diabetes and its Complications.

A person’s circadian rhythms — the natural, biological processes that follow a daily cycle and are found in most living beings — play an important role in the regulation of energy and body weight. Disruptions of these rhythms,  like shift work or eating lots of food high in fats, are connected to developing  such ills as type 2 diabetes mellitus, high cholesterol, and cardiovascular disease.

Melatonin, the hormone that induces sleepiness, is well-known for regulating circadian rhythms, and as such is called chronobiotic. Melatonin is also known to play a central role in the regulation, production, and breakdown of adipose (fat) tissue.

The effects of melationin are induced by two protein receptors, melatonin receptor 1 (MT1, coded by the MTNR1A gene) and melatonin receptor 2 (MT2, coded by MTNR1B).

The variant rs10830963 is one of the single nucleotide polymorphisms (SNPs) — changes in a single nucleotide, the building blocks of DNA — recently identified in the MTNR1B gene. It has been associated with altered circadian rhythm and melatonin actions, and with type 2 diabetes and body weight.

Researchers in Spain evaluated the effect of alterations in rs10830963 on changes in body weight and insulin resistance in response to two different diets — a high protein/low carbohydrate diet (HP diet) and a standard severe hypocaloric diet (low calorie, S diet) — given  over nine months.

A total of 270 people with obesity were included in the study, with a mean age 49.4. Their mean body mass index (BMI) was 35.1 kg/m2 (18.5 to 24.9 is considered normal) and their mean weight was 91.8 kg (about 202 lbs).

Each person inherits two alleles (or copies) of each gene, one from each parent. In the case of the rs10830963 mutation, the G allele — which means having a guanine nucleotide (a building block of DNA and RNA) in the mutated spot — is the gene copy previously linked with body weight.

Among the people, 143 (52.9%) did not have the G allele (both copies were C, for cytosine), 105 had one copy of the G allele (38.9%), and 22 patients had two G allele copies in rs10830963 (8.2%).

Results of CG and GG groups were combined, with CC analyzed separately. Patients were assigned to one of the diets, with 137 to the HP diet and 133 to the S diet. Baseline calorie intake was identical in both diets.

In both diet groups, improvements were seen in fat-related measurements (weight, waist circumference, and BMI) and in lower blood pressure. This change was greatest in non-G allele carriers (CC group).

After weight loss with either diet, total cholesterol, LDL-cholesterol, insulin, triglycerides and insulin resistance improved (decreased) only in the CC group. Both diet groups had a significant decrease in blood levels of leptin, a hormone that decreases appetite.

These findings “showed the association of rs10830963 MTNR1B polymorphism [variant] with body weight loss induced by two different hypocaloric diet and provided additional evidence on metabolic response such as cholesterol, insulin resistance and fasting insulin levels,” the scientists wrote.

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