Figure 7: High-fat feeding upregulates JAK2–PI3K signalling.

(a,b) Body weight and calorie intake of animals fed NCD (control, n=15 animals) and HFD (n=18 animals) after 3 weeks. There was no difference between control (NCD) and HFD animals. NCD, normal chow diet; HFD, high-fat diet. (c) Ratio of fat tissue to lean mass for control (n=10 animals) and HFD (n=14 animals) groups. High-fat feeding significantly increased the ratio of fat tissue to lean mass. (d–f) Plasma glucose, leptin and insulin levels after 3 weeks on HFD. Plasma glucose and leptin levels were significantly elevated in animals fed HFD (glucose, n=8 animals; leptin, n=14 animals) compared with control (glucose, n=7 animals; n=16 animals). However, insulin levels were similar in both groups. (g,h) Images of fluorescence microscopy showing the co-expression of pS6 (red) and POMC neurons (green) in the ARC of animal injected with leptin (g). Summary plot (h) showing the percent of pS6-positive POMC neurons in animals fed a NCD (n=9 animals) and a HFD (n=8 animals). There was a significant increase in the number of pS6-positive POMC neurons in animals fed HFD. Scale bar, 50 μm. S, saline; L, leptin. (i,j) PI3K p110α (i) and p110β (j) mRNA expression in POMC neurons. The dietary intervention significantly increased the expression of p110β, but not p110α, mRNAs in POMC neurons (p110α, NCD, n=6 neurons, HFD, n=5 neurons; p110β, NCD, n=6 neurons, HFD, n=9 neurons). (k) Calorie intake for control and HFD groups after microinjection of leptin into the MBH. High-fat feeding significantly diminished leptin’s anorexigenic effects (NCD, n=14 animals, HFD, n=18 animals). *P<0.05, **P<0.01, ***P<0.001 versus control (unpaired t-test); ^aP<0.05 versus NCD+leptin (unpaired t-test). All data are shown as mean±s.e.m.