MicroRNAs (miRNAs) are small noncoding RNAs approximately 22 nucleotides in length. Their main function is to regulate gene expression at the posttranscriptional level by inhibiting the translation of messenger RNAs (mRNAs). miRNAs originate in the cell nucleus from specific genes, where they can perform their function. However, they can also be found in serum, plasma, or other body fluids travelling within vesicles called exosomes and/or bound to proteins or other particles such as lipoproteins. miRNAs can form complexes outside the cell where they are synthesized, mediating paracrine and endocrine communication between different tissues. In this way, they can modulate the gene expression and function of distal cells. It is known that the expression of miRNAs can be affected by multiple factors, such as the nutritional or pathological state of the individual, or even in conditions such as obesity, insulin resistance, or after any dietary intervention. In this review, we will analyse miRNAs whose expression and circulation are affected in conditions of obesity and insulin resistance, as well as the changes generated after a dietary intervention, with the purpose of identifying new possible biomarkers of early response to nutritional treatment in these conditions.

Revista oficial de la Sociedad Española de Nutrición Parenteral y de la Sociedad Española de Nutrición. Está dedicada al estudio y divulgación de temas relacionados con la nutrición.

The loss of function melanocortin 4-receptor (MC4R) Ile269Asn mutation has been proposed as one of the most important genetic contributors to obesity in the Mexican population. However, whether patients bearing this mutation respond differently to weight loss treatments is unknown. We tested the association of this mutation with obesity in 1683 Mexican adults, and compared the response of mutation carriers and non-carriers to three different weight loss interventions: dietary restriction intervention, phentermine 30 mg/day treatment, and Roux-en-Y gastric bypass (RYGB) surgery. The Ile269Asn mutation was associated with obesity [OR = 3.8, 95% CI (1.5–9.7), p = 0.005]. Regarding interventions, in the dietary restriction group only two patients were MC4R Ile269Asn mutation carriers. After 1 month of treatment, both mutation carriers lost weight: −4.0 kg (−2.9%) in patient 1, and −1.8 kg (−1.5%) in patient 2; similar to the mean weight loss observed in six non-carrier subjects (−2.9 kg; −2.8%). Phentermine treatment produced similar weight loss in six carriers (−12.7 kg; 15.5%) and 18 non-carriers (−11.3 kg; 13.6%) after 6 months of pharmacological treatment. RYGB also caused similar weight loss in seven carriers (29.9%) and 24 non-carriers (27.8%), 6 months after surgery. Our findings suggest that while the presence of a single MC4R loss of function Ile269Asn allele significantly increases obesity risk, the presence of at least one functional MC4R allele seems sufficient to allow short-term weight loss in response to dietary restriction, phentermine and RYGB. Thus, these three different interventions may be useful for the short-term treatment of obesity in MC4R Ile269Asn mutation carriers.

Objective: Hepatic steatosis is associated with increased surgical complications in bariatric surgery patients. We aimed to evaluate the effect of phentermine in reducing hepatic steatosis, adipose tissue, and surgical complications in patients undergoing bariatric surgery. Methods: This was a two-arm, double-blind, randomized, controlled pilot trial of 64 adult subjects with BMI >35 kg/m2 selected for bariatric surgery randomized into phentermine group (15 mg once daily) or placebo group for 8 weeks. Both groups adhered to a hypocaloric diet (500 calories/day) and an individualized exercise program. The primary endpoint was reducing the frequency of hepatic steatosis measured by ultrasound and reducing adipose tissue through fat mass in total kilograms or percentage. Key secondary points were the prevalence of surgical complications. Baseline and final biochemical parameters and blood pressure too were assessments. Results: In the phentermine group, the frequency of hepatic steatosis decreased by 19%, and the percentage of patients with a normal ultrasound increased from 9% to 28% (p = 0.05). Likewise, the decrease in fat mass in kilograms was more significant in the phentermine group (56.1 kg vs. 51.8 kg, p = 0.02). A significant reduction in the HOMA-IR index was observed regardless of weight loss. No differences in surgical complications were observed between groups. Phentermine was well-tolerated; no differences were observed in the frequency of adverse events between the groups. Conclusions: Phentermine decreased the proportion of individuals with hepatic steatosis by 19% and promoted a more significant fat mass loss in kilograms among candidates for bariatric surgery.

The post-nutritional intervention modulation of miRNA expression has been previously investigated; however, post-acute dietary-ingestion-related miRNA expression dynamics in individuals with obesity and insulin resistance (IR) are unknown. We aimed to determine the acute effects of protein ingestion from different dietary sources on the postprandial metabolic response, amino acid levels, and circulating miRNA expression in adults with obesity and IR. This clinical trial included adults with obesity and IR who consumed (1) animal-source protein (AP; calcium caseinate) or (2) vegetable-source protein (VP; soy protein isolate). Glycaemic, insulinaemic, and glucagon responses, amino acid levels, and exosomal microRNAs isolated from plasma were analysed. Post-AP ingestion, the area under the curve (AUC) of insulin (p = 0.04) and the plasma concentrations of branched-chain (p = 0.007) and gluconeogenic (p = 0.01) amino acids increased. The effects of different types of proteins on the concentration of miRNAs were evaluated by measuring their plasma circulating levels. Compared with the baseline, the AP group presented increased circulating levels of miR-27a-3p, miR-29b-3p, and miR-122-5p (p < 0.05). Subsequent analysis over time at 0, 30, and 60 min revealed the same pattern and differences between treatments. We demonstrated that a single dose of dietary protein has acute effects on hormonal and metabolic regulation and increases exosomal miRNA expression in individuals with obesity and IR.

Circulating concentration of arginine, alanine, aspartate, isoleucine, leucine, phenylalanine, proline, tyrosine, taurine and valine are increased in subjects with insulin resistance, which could in part be attributed to the presence of single nucleotide polymorphisms (SNPs) within genes associated with amino acid metabolism. Thus, the aim of this work was to develop a Genetic Risk Score (GRS) for insulin resistance in young adults based on SNPs present in genes related to amino acid metabolism. We performed a cross-sectional study that included 452 subjects over 18 years of age. Anthropometric, clinical, and biochemical parameters were assessed including measurement of serum amino acids by high performance liquid chromatography. Eighteen SNPs were genotyped by allelic discrimination. Of these, ten were found to be in Hardy-Weinberg equilibrium, and only four were used to construct the GRS through multiple linear regression modeling. The GRS was calculated using the number of risk alleles of the SNPs in HGD, PRODH, DLD and SLC7A9 genes. Subjects with high GRS (≥ 0.836) had higher levels of glucose, insulin, homeostatic model assessment- insulin resistance (HOMA-IR), total cholesterol and triglycerides, and lower levels of arginine than subjects with low GRS (p < 0.05). The application of a GRS based on variants within genes associated to amino acid metabolism may be useful for the early identification of subjects at increased risk of insulin resistance.