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LGR signaling mediates muscle-adipose tissue crosstalk and protects against diet-induced insulin resistance

ABSTRACT: Obesity impairs tissue insulin sensitivity and signaling, promoting type-2 diabetes. Although improving insulin signaling is key to reversing diabetes, the multi-organ mechanisms regulating this process are poorly defined. We screened the secretome and receptome in Drosophila to identify the hormonal crosstalk affecting diet-induced insulin resistance and obesity. We discovered a complex interplay between muscle, neuronal, and adipose tissues, mediated by Bone Morphogenetic Protein (BMP) signaling and the hormone Bursicon, that enhances insulin signaling and sugar tolerance. Muscle-derived BMP signaling, induced by sugar, governs neuronal Bursicon signaling. Bursicon, through its receptor Rickets, a Leucine-rich-repeat-containing G-protein coupled receptor (LGR), improves insulin secretion and insulin sensitivity in adipose tissue, mitigating hyperglycemia. In mouse adipocytes, loss of the Rickets ortholog LGR4 blunts insulin responses, showing an essential role of LGR4 in adipocyte insulin sensitivity. Our findings reveal a muscle-neuronal-fat-tissue axis driving metabolic adaptation to high-sugar conditions, identifying LGR4 as a critical mediator in this regulatory network.

INSTRUMENT(S): Orbitrap Exploris 480

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Preadipocyte

DISEASE(S): Type 2 Diabetes Mellitus

SUBMITTER: Martin R. Larsen

LAB HEAD: Kim Rewitz

PROVIDER: PXD053061 | Pride | 2024-06-27

REPOSITORIES: Pride

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			Action	DRS
	AdipocytesPhosphoHpHfractions.msf	Msf
	Adipocytes_Phospho_HpHF01.mzML	Mzml
	Adipocytes_Phospho_HpHF01.raw	Raw
	Adipocytes_Phospho_HpHF02.mzML	Mzml
	Adipocytes_Phospho_HpHF02.raw	Raw

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