Figure 7.
2p23.3 lipodystrophy-like locus effect on mitochondrial fragmentation and lipid accumulation in visceral adipocytes
(A) PheWAS66 at the 2q23.3 risk locus shows associations with height, WHRadjBMI, T2D, and Calcium.
(B) LipocyteProfiler was performed in subcutaneous and visceral AMSCs of eight risk and six non-risk haplotype carriers across adipocyte differentiation (days 0, 3, and 14).
(C) In visceral AMSCs, 74 and 76 features were different between haplotypes at day 3 and day 14 of differentiation, respectively, with 70% of differential features at day 3 being mitochondrial and 80% lipid-related at day 14.
(D) Representative images of visceral AMSCs from risk (top) and non-risk (bottom) haplotype at day 3 of differentiation stained using LipocytePainting. Scale bars, 10 μm.
(E) Mito MaxIntensity and Mito Texture Entropy were higher at day 3 of differentiation in visceral AMSCs from six risk haplotype carriers, suggesting more fragmented and higher mitochondrial membrane potential. y axis shows LP units (normalized LP values across eight batches, see STAR Methods).
(F) Representative images of visceral AMSCs from risk (top) and non-risk (bottom) haplotype at day 14 of differentiation stained using LipocytePainting. Scale bars, 10 μm.
(G) LargeLipidObject MedianIntensity was lower and Lipid Texture AngularSecondMoment was higher at day 14 of differentiation in visceral AMSCs from six risk haplotype carriers, suggesting a perturbed lipid phenotype characterized by reduced lipid-droplet stabilization and/or formation. y axis shows LP units (normalized LP values across eight batches, see STAR Methods).