Evidence map›Paper›PMID 28839185›Full record

ArticleScientific reports2017

Antisense oligonucleotide and thyroid hormone conjugates for obesity treatment.

Yang Cao, Tomoko Matsubara, Can Zhao, Wei Gao, Linxiu Peng, Jinjun Shan, Zhengxia Liu, Fang Yuan, Lingyi Tang, Peixin Li and 5 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
2.2field-weighted citation impact, top 12% 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

7 citing papers in PubMed, 17 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

15 authors at 5 institutions in 3 countries.

Yang CaoDepartment of Medicine, Physiology and Biophysics, UC Irvine Diabetes Center, Center for Epigenetics and Metabolism, University of California Irvine, Irvine, California, 92697, USA.
Tomoko MatsubaraDepartment of Kinesiology & Physiology, East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, North Carolina 27834, USA.
Can ZhaoDepartment of Medicine, Physiology and Biophysics, UC Irvine Diabetes Center, Center for Epigenetics and Metabolism, University of California Irvine, Irvine, California, 92697, USA.
Wei GaoDepartment of Medicine, Physiology and Biophysics, UC Irvine Diabetes Center, Center for Epigenetics and Metabolism, University of California Irvine, Irvine, California, 92697, USA.
Linxiu PengMedical Metabolomics Center, Jiangsu Key Laboratory of Pediatric Respiratory Disease, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
Jinjun ShanMedical Metabolomics Center, Jiangsu Key Laboratory of Pediatric Respiratory Disease, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
Zhengxia LiuDepartment of Medicine, Physiology and Biophysics, UC Irvine Diabetes Center, Center for Epigenetics and Metabolism, University of California Irvine, Irvine, California, 92697, USA.
Fang YuanDepartment of Medicine, Physiology and Biophysics, UC Irvine Diabetes Center, Center for Epigenetics and Metabolism, University of California Irvine, Irvine, California, 92697, USA.
Lingyi TangDepartment of Medicine, Physiology and Biophysics, UC Irvine Diabetes Center, Center for Epigenetics and Metabolism, University of California Irvine, Irvine, California, 92697, USA.
Peixin LiDepartment of Kinesiology & Physiology, East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, North Carolina 27834, USA.
Zhibin GuanDepartment of Chemistry, University of California, Irvine, 92697, California, USA.
Zhuyuan FangDepartment of Cardiology, the First Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, China.
Xiang LuDepartment of Geriatrics, Sir Run Run Shaw Hospital, Nanjing Medical University, Nanjing, 211166, China.
Hu HuangDepartment of Kinesiology & Physiology, East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, North Carolina 27834, USA. huangh@ecu.edu.
Qin YangDepartment of Medicine, Physiology and Biophysics, UC Irvine Diabetes Center, Center for Epigenetics and Metabolism, University of California Irvine, Irvine, California, 92697, USA. qin.yang@uci.edu.
Nanjing University of Chinese Medicine · CNUniversity of California, Irvine · USEast Carolina University · USNanjing Medical University · CNJapan Society for the Promotion of Science · JP

Funding

Nicotinamide N-methyltransferase is a novel regulator of energy expenditureR01DK100385 · NIDDK · UNIVERSITY OF CALIFORNIA-IRVINE · PI YANG, QIN · 2014 to 2018
$1.7M
NIDDK NIH HHS R01 DK100385
6 · The paper itself

Abstract

Using the principle of antibody-drug conjugates that deliver highly potent cytotoxic agents to cancer cells for cancer therapy, we here report the synthesis of antisense-oligonucleotides (ASO) and thyroid hormone T3 conjugates for obesity treatment. ASOs primarily target fat and liver with poor penetrance to other organs. Pharmacological T3 treatment increases energy expenditure and causes weight loss, but is contraindicated for obesity treatment due to systemic effects on multiple organs. We hypothesize that ASO-T3 conjugates may knock down target genes and enrich T3 action in fat and liver. Two established ASOs are tested. Nicotinamide N-methyltransferase (NNMT)-ASO prevents diet-induced obesity in mice. Apolipoprotein B (ApoB)-ASO is an FDA approved drug for treating familial hypercholesterolemia. NNMT-ASO and ApoB-ASO are chemically conjugated with T3 using a non-cleavable sulfo-SMCC linker. Both NNMT-ASO-T3 (NAT3) and ApoB-ASO-T3 (AAT3) enhance thyroid hormone receptor activity. Treating obese mice with NAT3 or AAT3 decreases adiposity and increases lean mass. ASO-T3 enhances white fat browning, decreases genes for fatty acid synthesis in liver, and shows limited effects on T3 target genes in heart and muscle. Furthermore, AAT3 augments LDL cholesterol-lowering effects of ApoB-ASO. Therefore, ASO and hormone/drug conjugation may provide a novel strategy for obesity and hyperlipidemia treatment.

Indexed as

AnimalsAnimal StructuresBody WeightMice, ObeseObesityOligonucleotides, AntisenseThyroid HormonesTreatment OutcomeOligonucleotides, AntisenseThyroid Hormones

Identifiers

PMID28839185
PMCPMC5571112
OpenAlexW2750200306

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.