Table 3.
Targeted disruption of molecular targets involved in inflammation and its impact on insulin sensitivity, liver fat content, and inflammation in adipose tissue and liver in mice. Models were included if the transgenic mouse model did not have an adiposity phenotype.
| Target | Method | Diet (%Fat) Duration | Insulin Sensitivity | Adipose Inflammation | Liver Fat | Liver Inflammation | Ref |
|---|---|---|---|---|---|---|---|
| BLT-1 | WBKO | HFD (60%) 12 weeks |
↑ | ↓ | ↓ | ↓ | (435) |
| Cadherin-11 | WBKO | HFD (60%) 5–12 weeks |
↑ | ↓ | ↓ | n/a | (70) |
| Cap (Sorbs1) | WBKO | HFD (40% by wt) 6–8 weeks |
↑ | ↓ | ↓ | n/a | (271) |
| Catalase | WBKO | ND (18%) 21 weeks HFD (60%) 21 weeks |
↔ ↓ |
↑ (↑) |
n/a n/a |
n/a n/a |
(369) |
| CCL2 | AT Overexpression | ND (6% by wt) 8 weeks HFD (32% by wt) 8 weeks |
↓ ↓ |
↑
↔ ↑ |
↔ ↔ |
n/a n/a |
(218) |
| CCL2 | AT
Overexpression WBKO |
ND (n/a) 11 weeks HFD (56%) 12 weeks |
↓ ↑ |
↑ ↓ |
↑ ↓ |
n/a n/a |
(221) |
| CCR2 | WBKO | HFD (60%) 24 weeks |
↑ | ↓ | ↓ | n/a | (503) |
| CCR2 | Hematopoietic KO by BMT | HFD (60%) 20 weeks |
↔ | ↓ | n/a | (↓) | (159) |
| CD1d (iNKT) | WBKO | HFD (44%) 26 weeks |
↔ | ↔ | ↔ | ↔ | (289) |
| CD1d (iNKT) | WBKO | ND (10%), 19 weeks HFD (45%) 19 weeks |
↓ ↓ |
↔ ↑ ↔ |
↔ ↓ |
↔ ↑ |
(415) |
| CD1d (iNKT) | WBKO | HFD (60%) 4 days |
↓ | (↓) | n/a | ↔ | (207) |
| CD8 | Pharmacological inhibition | HFD (60%) 8 weeks |
↑ | ↓ | n/a | n/a | (345) |
| CD11c | BMT followed by selective depletion | HFD (60%) 16 weeks |
↑ | ↓ | ↓ | ↔ ↓ | (374) |
| CD18 | WBDNKI | HFD (45%) 20 weeks |
↓ | ↔ (↑) | n/a | ↑ | (303) |
| CD36 | Hematopoietic KO by BMT | HFD (42%) 20 weeks |
↔ | ↓ | n/a | n/a | (342) |
| CD95 (Fas) | Adipose KO | HFD (58%) 6 weeks |
↑ | ↓ | ↓ | (↓) | (520) |
| CXCR3 | WBKO | HFD (60%) 20 weeks |
↑ | ↓ | ↔ | n/a | (96) |
| CTRP7 | WBKO | HFD (60%) 12 weeks |
↔ | ↑ | ↔ | n/a | (376) |
| C5aR | WBKO | HFD (60%) 16–19 weeks |
(↑) | ↓ | ↔ | ↔ | (378) |
| Dab2 | Myeloid KO | HFD (60%) 12 weeks |
↑ | ↔ ↑ | n/a | n/a | (5) |
| FABP4 and FABP5 | WBKO BMT | HFD (60%) 15 weeks |
↑ | ↔ ↓ | (↔) | ↔ | (136) |
| Fetuin-A | WBKO | HFD (65%) 12 weeks |
↑ | ↓ | n/a | n/a | (361) |
| GPR120 | WBKO | ND (14%) 15–20 weeks HFD (60%) 15 weeks |
↓ ↔ |
↑ ↔ |
↔ ↔ |
↔ ↔ |
(354) |
| HIF-1α | Adipose KO | HFD (60%) 10 weeks |
↑ | ↓ | ↓ | ↓ | (267) |
| HIF-2α | WBKO (+/−) | HFD (60%) 16 weeks |
↓ | ↑ | n/a | n/a | (76) |
| Id3 | Lymphoid KO | HFD (60%) 12 weeks |
↔ | ↔ ↓ | n/a | n/a | (170) |
| Immunoglobulin μ heavy-chain | WBKO (B cell depletion) |
HFD (60%) 16 weeks |
↑ | ↔ ↓ | n/a | n/a | (511) |
| IR | Myeloid KO | HFD (55%) 12 weeks |
↑ | ↓ | n/a | ↔ | (297) |
| IFNγ | WBKO | HFD (60%) 13 weeks |
↑ | ↔ | n/a | ↓ | (350) |
| IL-10 | BMT WBKO | HFD (56%) 12 weeks |
↔ | ↔ | n/a | ↔ | (251) |
| Jα18 (iNKT) | WBKO | HFD (60%) 12–20 weeks |
↑ | ↓ | ↓ | ↓ | (519) |
| Jα18 (iNKT) | WBKO | HFD (32%) 18 weeks |
↔ | ↔ | ↔ | ↔ | (409) |
| JNK1 | Hematopoietic KO by BMT | HFD (60%) 20 weeks |
↑ | ↓ | ↔ | ↓ | (430) |
| JNK1 | Hematopoietic KO by BMT | HFD (60%) 26–36 weeks |
↑ | ↔ (↓) | ↔ | ↔ | (481) |
| JNK1 | Adipose KO | HFD (60%) 16 weeks |
↑ | ↔ ↓ | ↓ | ↔ | (403) |
| JNK1 | Muscle KO | HFD (60%) 16 weeks |
↑ | ↑ | ↑ | (↑) | (404) |
| JNK1 | Myeloid KO | HFD (60%) 4 weeks |
↑ | ↓ | n/a | ↓ | (165) |
| NAMPT | Adipose KO | ND (13%) 12–20 weeks |
↓ | ↑ | ↑ | ↔ | (446) |
| NLRP3 | WBKO | HFD (60%) 6 weeks |
↑ | ↓ | ↓ | n/a | (486) |
| Osteopontin | WBKO | HFD (60%) 25 weeks |
↑ | ↓ | n/a | n/a | (346) |
| Osteopontin | Mostly visceral ATM in ob/ob mice | ND (n/a) 5–7 weeks |
↑ | ↔ (↓ osteopontin in visceral ATM) |
n/a | ↔ | (22) |
| PDCD4 | WBKO | ND (n/a) 24 weeks |
↔ | ↔ | ↔ | ↔ | (500) |
| SR-A | WBKO | HFD (58%) 16 weeks |
↓ | ↔ | n/a | n/a | (552) |
| Sema3e | WBKO Overexpression |
HFHS (n/a) 8 weeks ND (n/a) 8 weeks |
↑ ↓ |
↓ ↑ |
n/a n/a |
n/a ↑ |
(425) |
| SOCS1 | Myeloid KO | ND (n/a) 12–15 weeks |
↓ | ↑ | n/a | ↑ | (405) |
| TNFα | Mostly visceral ATM in ob/ob mice | ND (n/a) 5–7 weeks |
↑ | ↔ (↓TNFα in visceral ATM) |
↔ | ↔ | (22) |
| TLR2 | WBKO | HFD (58%) 20 weeks |
↑ | ↓ | ↓ | ↓ | (104) |
| TLR4 | WBKO | HFD (60%) 16 weeks |
↑ | ↔ (↓) | n/a | n/a | (448) |
| TLR4 | WBKO | HFD (42%) 22 weeks |
↑ | ↓ | ↓ | (↓) | (380) |
| TLR4 | Hematopoietic KO by BMT | HFD (n/a) 16 weeks |
↑ | ↓ | ↓ | ↓ | (402) |
| TLR4 | WBKO | HFD (60%) 12 weeks |
↑ | ↔ | ↔ | n/a | (502) |
| TLR4 | WBKO | HFD (65%) 12 weeks |
↑ | ↓ | n/a | n/a | (361) |
| TLR4 | Liver KO | HFD (42%) 12 weeks |
↑ | ↓ | ↓ | ↓ | (208) |
| TLR9 | WBKO | HFD (60%) 12 weeks |
↑ | ↓ | n/a | n/a | (344) |
Abbreviations: AT, adipose tissue; ATM, adipose tissue macrophage; BLT-1, Leukotrin B4 receptor-1; BMT, bone marrow transfer; Cap, Cbl-associated protein (Sorbs1); C5aR, complement anaphylatoxin C5a receptor; CCL2, C-C motif chemokine ligand 2 (MCP1); CCR2, C-C motif chemokine receptor type 2; CD, cluster of differentiation; CXCR3, C-X-C motif chemokine receptor 3; CTRP7, C1q/TNF-related protein 7; Dab2, disabled homolog 2; FABP, fatty acid-binding proteins; GPR120, G protein-coupled receptor 120; GH-R, growth hormone-receptor; HFD, high-fat diet; HFHS, high-fat high-sucrose diet; HIF, hypoxia-inducible factor; iNKT, invariant natural killer T cell; IR, insulin receptor; IFNγ, interferon-γ; IL, interleukin; JNK1, c-Jun NH2-terminal kinase-1; KO, knockout; NAMPT, nicotinamide phosphoribosyl-transferase; ND, normal diet (chow); NLRP3, nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing 3; PDCD4, programmed cell death-4; Sema3e, Semaphorin E; SOCS1, suppressor of cytokine signaling-1; SR-A, class A scavenger receptor; TLR, toll-like receptor; WBKO, whole body knockout; WBDNKI, whole body dominant negative knock-in