Figure 5: MMP11 deficiency promotes diabesity.

(a) Increased body weight in 8- and 30-week-old Mmp11−/− mice compared to age-matched WT counterparts (n = 10/group); (b) IPGTT test in Mmp11−/− and WT mice (n = 8/group); (c) IPIST test in Mmp11−/− and WT mice (n = 8/group); (d) Circulating adiponectin, leptin and IGF1 levels in Mmp11−/−and WT mice (n = 8/group); (e) Toluidine blue staining (upper panels) and ultrastructure (lower panels) of WAT and BAT. Semi-thin sections (scale bar = 50 μm) and TEM (scale bar = 10 μm) showed hypertrophied white adipocytes in Mmp11−/− mice compared to WT mice. Mmp11−/− brown adipocytes accumulate more fat than WT cells; (f) Metabolic gene expression profile changes in the WAT of Mmp11−/− and WT mice (n = 5–7/group); (g) Summary of the metabolic abnormalities observed in Mmp11-Tg and Mmp11−/− mice; (h) A proposed model of the MMP11-induced metabolic switch from mitochondrial respiration to aerobic glycolysis. MMP11 induces an increase in IGF1 bioavailability. The subsequent increase in the IGF1/AKT signalling provokes an increase in oxidative stress (ROS) which impairs mitochondrial respiration (OXPHOS), and an increase in aerobic glycolysis producing lactate that can be used as a complementary source of energy for the cell itself or for neighboring cells via the MCT4/MCT1 shuttle. Fatty acid oxidation is also increased and represents a metabolic fuel as well. TCA: tricarboxylic acid cycle.