The mitochondrial‐derived peptide MOTS‐c is a regulator of plasma metabolites and enhances insulin sensitivity

Figure 1. Characteristics of MOTS‐c injected diet‐induced obese (DIO) mice. C57BL/6J mice (17‐weeks old) were fed a high‐fat diet starting at 5 weeks of age. MOTS‐c peptide injections (2.5 mg/kg; IP; BID) were performed for 3 days. (A) Body weight, food intake, insulin, leptin, and (B) Blood glucose levels were measured. Data are reported as mean ± SEM of six mice per group. * P < 0.05.

Figure 2. The selected plasma metabolites differences between water and MOTS‐c injected DIO mice were distinct. (A) Variance percentage scree plots (B) 2D individuals factor map (C) 2D variables factor map.

Figure 3. MOTS‐c administration decreases S1P levels in the plasma. (A) Schematic diagram of sphingolipid metabolism (B) Sphingomyelin and (C) sphingosine 1‐phosphate (S1P) levels in plasma from DIO mice injected with either water or MOTS‐c (N = 6/group) Data are reported as mean ± SEM of six mice per group. * P < 0.05.

Figure 4. Fat accumulation in the muscle decreased suggesting reduced metabolic dysfunction. The mRNA expression levels of (A) ANGPTL3, (B) ANGPTL4, and (C) ANGPTL8 in water and MOTS‐c injected DIO mice muscle. (D) The pathways involved in monoacylglycerol biogenesis. Data are reported as mean ± SEM of six mice per group. * P < 0.05.

Figure 5. Omega oxidation is decreased in MOTS‐c–injected mice liver. (A) The dicarboxylic acid biosynthesis via omega oxidation. (B–D) The mRNA expression of the genes involved in the omega oxidation pathways in the liver. Data are reported as mean ± SEM of six mice per group. * P < 0.05.

Figure 6. Folate cycle did not change in MOTS‐c injected DIO mice compared to control (A) The folate cycles and its related pathways. (B) The mRNA levels of MTR in the skeletal muscle.