Table 2. Comparison of human MFN2R707W-associated lipodystrophy with phenotype of Mfn2R707W/R7007W mice.
BAT, brown adipose tissue; GTT, glucose tolerance test; HFD, high-fat diet; ISR, integrated stress response; MFN2, mitofusin 2; mRNA, messenger ribose nucleic acid; mtDNA, mitochondrial DNA; PLIN1, perilipin 1; TEM, transmission electron microscope; WAT, white adipose tissue.
| Human | Phenocopy? | Mouse |
|---|---|---|
| Upper body adipose overgrowth | No | No difference in weight of any adipose depots |
| Lower limb lipoatrophy | No | |
| Insulin resistance | No | No difference on GTT or fasting insulin |
| Lower serum leptin concentration | Yes | Seen on chow or HFD; lower secretion seen from adipose explants |
| Severely reduced adipose leptin mRNA expression | Partial | Modest decrease only; only significant in some analyses |
| Lower serum adiponectin concentration | Yes | Seen on chow or HFD; lower secretion seen from adipose explants |
| Severely reduced adipose adiponectin mRNA expression | Yes | Seen on chow or HFD and in adipose explants |
| No change in WAT MFN2 protein expression (only over-grown WAT studied) | Yes | No difference in any tissue studied, though variable in WAT and BAT. |
| No difference in adipocyte size | Yes | True on both chow and HFD |
| Disorganised, fragmented WAT mitochondria on TEM | Partial | More circular mitochondria with trend towards reduced cristae |
| Upregulation of nuclear and down regulation of mitochondrial Oxphos transcriptional pathway | Yes | True in inguinal and epididymal WAT, and BAT |
| Lower Oxphos complex II and III but preserved complex I and IV protein | Partial | Lower complex I and IV protein in WAT |
| Lower WAT mtDNA | Partial | Lower mtDNA in BAT but not WAT |
| Transcriptional activation of ISR | Yes | Seen in inguinal and epididymal WAT, and BAT |