Table 2 Regulatory roles of inflammatory factors in systemic metabolic reprogramming

IL1

IL1R1, IL1R2

Inhibit food intake; promote protein and fat decomposition; enhance IL6 expression

Promoting α-MSH release from POMC neurons; stimulating hypothalamic neurons to release CRH

^350,351,353

IL4

IL4Rα, IL13Rα, γc

Inhibit adipogenic differentiation of FAPs by insulin; prevent fatty degeneration of muscle; promote clearance of injured muscle fibers

Activating the STAT6 signaling pathway

^366,367

IL6

IL6Rα, gp130

Inhibit myofibril synthesis and stimulate muscle breakdown; promote lipolysis and browning; massive liver hypertrophy and APR; splenomegaly; neuroinflammation; cardiac dysfunction and wasting

Activating the STAT signaling pathway; increasing the expression of Atrogin1; inhibiting phosphorylation of mTOR, EIF4EBP1, and RPS6 kinases

^{360,362,363,527}

IL20

IL22R1, IL20R2

Loss of adipose tissue

Enhancing PD-L1 via IFN-α; promoting macrophage infiltration to adipose tissue; increasing expression of ATGL and HSL

³⁶⁸

TNFα

TNFR

Promote lipolysis; inhibit protein synthesis and promote muscle atrophy; weaken muscle strength

Inhibiting LPL expression; enhancing ATGL activity; activating the NF-κB signaling pathway; promoting ROS generation; activating the UPS; activating the AMPK pathway; inhibiting the PI3K/Akt pathway

^371,372,528

TGFβ

TGFβR1, TGFβR2

Stimulate profibrotic muscle; inhibit muscle function recovery; promote skeletal myogenesis

Reversing the IGF-1/PI3K/Akt hypertrophy pathway by inhibiting Akt phosphorylation; inducing smad2/3/4 complex; regulating skeletal muscle oxidative metabolism

^{376,379,529,530}

OSM

OSMR, gp130, LIFR

Promote muscle atrophy; stimulate lipolysis and inhibit adipocyte insulin response

Activating the JAK/STAT signaling pathway; inducing amyotrophic-related genes expression; increasing EDA2R expression

^382,531

LIF

LIFR, gp130

Elevate lipolysis; induction of muscle atrophy; appetite suppression

Activating JAK/STAT3, PI3K/Akt/mTOR and MAPK signaling pathways; stimulating α-MSH release; increasing leptin expression

^353,387,390

GDF15

GFRAL, ALK1, ALK5

Regulate vagal sympathetic nervous system, inhibit appetite; enhance ATGL-dependent sympathetic nerve activation of adipose tissue lipolysis; promote osteoclast differentiation

Activating Smad pathway, PI3K/Akt signaling pathway and NF-κB signaling³⁸⁷ pathway; promoting activation of RET oncogene; activating HPA axis; promoting the expression of MuRF1 and MAFbx/atrogin-1

^{155,398,532,533,534}

IFNγ

IL28Rα, IL10Rβ

Accelerate protein degradation; suppression of appetite

Activating JAK/STAT signaling pathway; promoting inflammatory response

^1,11,345

LCN2

MC4R, SLC22A17

Suppress appetite; activation of immune cells; promote lipolysis

Activating cAMP and MC4R signaling in the hypothalamus; inducing the ferroptosis

^{66,67,301,535}