Table 2. Major functions involved in diet effect, proneness to obesity, resistance and adaptation to the obesogenic effects of a HFD.
Obesity resistance specific | Obesity proneness specific | Maternal effect : lean versus obese | Diet effect | |
Circulating fatty acids | ||||
(−) C16∶0, in OR2 only | (−) C16∶1 n-7, in all; (+) C18∶2 n-6, C20∶4 n-6 in OP1, OP2, with OP1> OP2; (+) C20∶4 n-6, OP1<OR1<OP2 not OR2; (+) C18∶0, C22∶6 n-3, in OP1 only | (+) Total fatty acid, in OP1, OR1 only; (−) C16∶0, in OR2 only; (+) C18∶2 n-6, C20∶4 n-6, OP1> OP2; (+) C20∶4 n-6, OP1<OR1<OP2 not OR2 | (−) C16∶1 n-7, in all; = C18∶1 n-3, in all | |
Liver transcriptome Metabolism | ||||
Lipid uptake, storage and accumulation, metabolism, utilization | (−) Acaca, Scd1, ApoA5, Cpt1, Ucp3, Pdk4, Fabp5, (by Ppara) in OR2; (−) Angptl4, Fabp4, Fabp3, Acadl, Cav1, Acads, Ucp2, Rxra, Fads2, in OR2 | (−) Plin3, Timp3, Lpin1, Lpin2, in OP with OP2>OP1 | (−) Apoa5, Fabp5, Hnf4a, Lepr, Scd1, Slc1a3; (+) Accn1, Fabp2 with OP>OR | |
Insulin signaling and sensitivity | (+/−) Pten, Ptpn1, Inppl1, Pik3r1, Bdnf, Slc2a4 (Glut4), in OR2 compared to OP2 | (−) Irs2, Pi3kr, Pi3kca, Hnf4a, in OP1, OP2 | ||
TG synthesis and lipid accumulation | (−) Rxra, ApoA5, Angptl4, Scd1, Lpin1, in OP1, OP2 | |||
Lipogenesis | (+) Fads2, Insig1, Ppargc1a, Srebf1, in OP1 | (+/−) Fads2, Insig1, Ppargc1a, Srebf1, (+) in OP1 (−) OP2, OR2 | ||
Lipid regulation and hepatic glucose production | (−) Insr, Cebpa, G6pc, Fasn, Pde3b, Scarb1, Eno2, in OP1 not in OP2, OR2 | |||
Fatty acid oxidation | (+) Acaca, Acads, Adrb1, Adrb3, Fabp2, Cpt1, Ppard, Ucp3, in OP2 but not OP1 | |||
Diverse | (−) Retn, Npy5r, Ppara, Pdk4, Pten, in OP2 and OR2 not in OP1 | |||
Liver transcriptome Neurotransmission | ||||
Calcium signaling | (−) Adora2b, Caca1s, Chrm1, Camk4, CckAr, CckBr, in OP1 to OP2 transition | |||
Thyroid signaling | (+/−)(+) Thrb, Ucp1, Pax8, Ucp3, Adrbr3, in OR2 | (+/−) (−) Thrb, in OP | ||
K+ channels: | (+/−)(−) Kcna2, Kcna3, Kcnd2, Kcnd3, Kcnj11, in OR2 | (+/−) (+) Kcna2, Kcna5, Kcna6, Kcnh3, Kcnj14, in OP | (−) Kcna7, Kcnh3, Kcnj4, Kcns1, Kcna1, Hcn1, in OP1 to OP2 transition; (+) Kcna7, Kcnh9, Kcnj4, Kcnj1, Kcna1 in OP and (−) or ( = ) in OP2 and OR2 | |
Serotonin receptors | (+/−)(−) Htr2c, Htr2b, Htr3b, Htr7, in OR2 | (+/−)(+) Htr3a, Htr3b, Htr7, Htr1b, in OP1 and (−) or ( = ) in OP2 and OR2 | ||
Cholinergic/Nicotinic Receptors | (−) Chrb2, Chrne, Chrna6, in OR2; +/−) Chrm3, (+) in OR compared with OP; (−) (+) Chrm3, Chrnb2, Chrnd | (+/−) (+) Chrm3, Chrnb2, Chrnd, in OP1, OP2; (+) Chrna1, Chrm4, Chrne, in OP1 and (+) or = in OP2, OR2 | (+) Chrna1, Chrm4, Chrne, in OP1 and (−) or ( = ) in OP2, OR2 | |
Orexigenic | (+/−) (−) Npy, AgRP, Hcrt, Npy5r, Npy1r in OR | (+/−) (+) Npy, AgRP, Hcrt, Npy5r, Npy1r in OP | ||
Anorexigenic | (+) Mc4r, Mc5r, Sst, in OR2 compared to OP2 | (+/−) (−) Mc4r, Mc5r, Sst, in OP2 compared to OR2 | ||
GABA receptors : | (+) Gabra2, Gabrb3, Gabrd, Gabrg2, Gabrg3, Gabrq, Gabrr2, in OR2 | |||
Liver transcriptome imprinted genes | ||||
Imprinted genes from different clusters: | (+/−) Gnas, Gtl2, Mas1, Nnat, between OP2, OR2; (-) Igf2r, Gtl2 in 0R2 | (+/−) Gnas, Gtl2, Mas1, Nnat between OP2, OR2; (+) Slc22a18, Xist, Nfs1, Gtl2, (−) Gnas-Gsa, in OP1, OP2 | (−) Ins2, Kcnq1ot, Gabrg3 in OP2, OR2 not in OP1 | |
PWS cluster | (+/−) Ipw, Pwcr1, between OP2 and OR2; (+) (+) Snrpn, Gabrb3, Gabrg3, in OR2 | (+/−) Ipw, Pwcr1, in 0P1, OP2 compared to OR2 | (−) Gabrg3, in OP2, OR2 not in OP1 | |
BWS cluster | (+) Ascl2, Igf2-as; (−) Slc22a18, Kcnqt1, Kcnqt1ot, Cdkn1c, Igf2, Ins2, Cdkn1 in OR2 | (+) Kcnq1 in OP1, OP2, | (−) Ins2, Kcnq1ot, in OP2, OR2 not in OP1 | |
Adipose tissue Gene expression | ||||
Adipogenesis, lipid storage Adipocyte size hypertrophy/hyperplasia | (−) Lep, Peg1, in OP2, OR2 | (+) Lep, Peg1, in OP1 | ( = ) normalization of adipocyte size, in OP2 compared to OP1 | |
Energy expenditure | (+/−) Adrb3 in OP1 and OP2 compared to OR2 | (−) Ucp1, | ||
Glucose utilisation | (+/−) Pdk4 (−) in OP1, (+) in OR1, OP2, OR2 | (+/−) Pdk4 (+) in OP1, (+) in OR1, OP2, OR2 | (−) Glut4, Pparg | |
Lipogenesis | (−) Scd1 | |||
Lipolysis | (−) Acc1 | |||
Liver epigenetic marks | ||||
Global DNA methylation | (−) in OP1 only | (−) in OP1 only | ||
Histone K-acetylation | ||||
Histone methylation | (+) H3K4me3, in OP2, OR2 | |||
Liver epigenetic machinery | ||||
DNA methylation | (+) Dnmt2, in OP2,OR2 only | |||
Histone K-acetylation | (+) Hat1, in OP2 only | |||
Histone K-deacetylation | (+) Hdac5, in OR1 only | (+) Hdac5, in OR1 | ||
Histone methylation | (−) H3K9ac, in OR2 | (+) Suv39h1, Suv39h2, in OP1 only | (+) Suv39h1, Suv39h2, in OP1 only | (−) Set7/9 |
Histone K-demethylation | (−) H3K9me1, in OR2 | (−) Jhdm2a, in OP2, OR2 | ||
Muscle epigenetic marks | ||||
Global DNA methylation | (−) in OP2 only | (−) in OP2 only | ||
Muscle epigenetic machinery | ||||
DNA methylation | (+/−) Dnmt2 in F2, (+) in OR2, (+) in OP2/CD | (+/−) (+) Dnmt2, in OP1, OR1, OR2, (+/−) (+) in OP2 | ||
Histone K- acetylation | (+) Hat1, in OP2 only | (+) Hat1, in OP2 only, (+) Gcn5, in OP1, OR1 only | (+) Gcn5, in OP1, OR1 only | |
Histone K-deacetylation | (+) Hdac5, in OR1 only | (+) Hdac5, in OR1 only | ||
Histone K-methylation | (+) Suv39h1, in OP1, OR1, OR2 only; (+) Suv39h2, in OR1, OR2 only | |||
Histone K-demethylation | (−) Jhdm2a, in OP2, OR2, OP2<OP2 |
(+/−) mirror-image pattern of gene expression; (−) decrease in gene expression; (+) increase in gene expression; ±dysregulated gene expression (either up- or downregulation).