Evidence map›Paper›PMID 34183373›Full record

ArticleDiabetes2021

Deletion of the Feeding-Induced Hepatokine TSK Ameliorates the Melanocortin Obesity Syndrome.

Qiuyu Wang, Peng Zhang, Isin Cakir, Lin Mi, Roger D Cone, Jiandie D Lin

Open access · bronzeAbstract read
In one paragraph

Article in Diabetes, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
0.8field-weighted citation impact, top 34% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed, 12 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

Qiuyu WangLife Sciences Institute and Department of Cell & Developmental Biology, Michigan Medicine, University of Michigan, Ann Arbor, MI.
Peng ZhangLife Sciences Institute and Department of Cell & Developmental Biology, Michigan Medicine, University of Michigan, Ann Arbor, MI.
Isin CakirLife Sciences Institute and Department of Molecular & Integrated Physiology, Michigan Medicine, University of Michigan, Ann Arbor, MI.
Lin MiLife Sciences Institute and Department of Cell & Developmental Biology, Michigan Medicine, University of Michigan, Ann Arbor, MI.
Roger D ConeLife Sciences Institute and Department of Molecular & Integrated Physiology, Michigan Medicine, University of Michigan, Ann Arbor, MI.
Jiandie D LinLife Sciences Institute and Department of Cell & Developmental Biology, Michigan Medicine, University of Michigan, Ann Arbor, MI jdlin@umich.edu.ORCID 0000-0001-8069-5647
Michigan Medicine · USUniversity of Michigan · US

Funding

Regional Pilot And Feasibility Study Grants ProgramP30DK020572 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Mehboob A Hussain · 2013 to 2026
$24.3M
University of Michigan Center for Gastrointestinal ResearchP30DK034933 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI OMARY, BISHR · 1986 to 2021
$22.5M
Pilot and Feasibility (P and F) ProgramP30DK089503 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Kanakadurga Singer · 2010 to 2026
$20.3M
Melanocortin Signaling in Feeding BehaviorR01DK070332 · NIDDK · VANDERBILT UNIVERSITY · PI CONE, ROGER D. · 2004 to 2017
$6.1M
Metabolic crosstalk through brown fat-enriched secreted factorsR01DK102456 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Jiandie D Lin · 2015 to 2026
$4.9M
Hepatokine Regulation of Thermogenesis and Metabolic PhysiologyR01DK118731 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI LIN, JIANDIE D · 2019 to 2022
$1.6M
NIDDK NIH HHS P30 DK020572NIDDK NIH HHS P30 DK034933NIDDK NIH HHS P30 DK089503NIDDK NIH HHS R01 DK070332NIDDK NIH HHS R01 DK102456NIDDK NIH HHS R01 DK118731
6 · The paper itself

Abstract

Work in recent decades has established that metabolic hormones released by endocrine cells and diverse other cell types serve to regulate nutrient intake and energy homeostasis. Tsukushi (TSK) is a leucine-rich repeat-containing protein secreted primarily by the liver that exerts an inhibitory effect on brown fat sympathetic innervation and thermogenesis. Despite this, physiological regulation of TSK and the mechanisms underlying its effects on energy balance remain poorly understood. Here we show that hepatic expression and plasma concentrations of TSK are induced by feeding and regulated by melanocortin-4 receptor (MC4R) signaling. We generated TSK and MC4R-double-knockout mice to elucidate the nature of cross talk between TSK and the central regulatory circuit of energy balance. Remarkably, TSK inactivation restores energy balance, ameliorates hyperphagia, and improves metabolic health in MC4R-deficient mice. TSK ablation enhances thermogenic gene expression in brown fat, dampens obesity-association inflammation in the liver and adipose tissue, and protects MC4R-null mice from diet-induced nonalcoholic steatohepatitis. At the cellular level, TSK deficiency augments feeding-induced c-Fos expression in the paraventricular nucleus of the hypothalamus. These results illustrate physiological cross talk between TSK and the central regulatory circuit in maintaining energy balance and metabolic homeostasis.

Indexed as

Adipose Tissue, BrownAdipose Tissue, Whitealpha-MSHAnimalsAnti-Obesity AgentsEnergy MetabolismHypothalamusLiverMiceMice, KnockoutNon-alcoholic Fatty Liver DiseaseObesityProteoglycansReceptor, Melanocortin, Type 4Signal TransductionThermogenesisalpha-MSHAnti-Obesity AgentsProteoglycansReceptor, Melanocortin, Type 4setmelanotidetsukushi protein, mouse

Identifiers

PMID34183373
PMCPMC8576423
OpenAlexW3173492831

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.