Methods for identification, assessment, prevention, and treatment of metabolic disorders using SLIT2
Inventors
Spiegelman, Bruce M. • Svensson, Katrin J.
Assignees
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Publication Number
US-12702694-B2
Publication Date
2026-08-11
Expiration Date
Abstract
The present invention relates to methods for identifying, assessing, preventing, and treating metabolic disorders and modulating metabolic processes using Slit2.
Core Innovation
The disclosure describes a method for detecting an agent that modulates Slit2 expression or activity to increase a metabolic response in a subject. It identifies Slit2 as a PRDM16-regulated protein secreted by beige adipocytes and characterizes Slit2-C as an approximately 50 kDa C-terminal cleavage fragment. The screening result identifies that Slit2-C expression or activity is significantly lower in a pre-contact sample than in a post-contact sample via antibody detection.
Slit2-C binds adipocyte cell surfaces and promotes thermogenic gene expression and respiration, linking the beige-fat-derived modulator to energy expenditure and glucose homeostasis. Increased circulating Slit2-C raises energy expenditure, enhances tissue oxygen consumption, and improves glucose tolerance in diet-induced obese mice. The disclosure further encompasses monitoring Slit2-based interventions for metabolic disorders, cellular respiration, and thermogenic response regulation without significantly altering body weight.
Claims Coverage
The claims define one independent claim directed to detecting an agent modulating Slit2, comprising three inventive features across independent and dependent claims.
Comparative detection of Slit2-C
The independent claim covers detecting an agent that modulates Slit2 expression or activity for increasing a metabolic response in a subject by determining whether Slit2-C expression or activity is significantly lower in a first sample prior to agent contact than in at least one subsequent sample, using an antibody that detects Slit2-C and detecting association between Slit2-C and the antibody.
Specified metabolic response measures and markers
Dependent claims specify metabolic responses including changes in marker expression or activity, adipose-cell function, respiration, whole-body oxygen consumption, obesity or appetite, insulin secretion, glucose tolerance, phosphorylation, and UCP1 protein expression, with markers including UCP-1, CIDEA, PGC1α, and type II deiodinase.
Agent forms, sample types, and quantitative decrease refinements
Dependent claims identify agents comprising a nucleic acid molecule encoding a Slit2 polypeptide or fragment, a Slit2 polypeptide or fragment, or a small molecule binding Slit2; sample types including tissue, blood, serum, plasma, saliva, urine, stool, and bone marrow; and define significantly lower expression or activity as at least 25% lower.
The claims center on comparative antibody-based detection of Slit2-C expression or activity before and after agent contact, with dependent claims defining associated response measures, markers, agent forms, sample types, and a quantitative decrease threshold.
Stated Advantages
Slit2-C is associated with thermogenic gene expression, increased tissue oxygen consumption, and raised energy expenditure.
Slit2-C is associated with improved glucose tolerance and glucose homeostasis in diet-induced obese mice.
Documented Applications
Detecting or monitoring an agent that modulates Slit2 expression or activity for increasing a metabolic response in a subject by assessing Slit2-C in samples obtained before and after agent contact.
Assessing metabolic responses comprising changes in marker expression, adipose-cell function, respiration, whole-body oxygen consumption, obesity, appetite, insulin secretion, glucose tolerance, phosphorylation, and UCP1 protein expression.
Slit2-based interventions and efficacy assessments for metabolic disorders, adipose thermogenesis, energy expenditure, glucose homeostasis, cellular respiration, and insulin secretion.
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