Evidence mapPaperPMID 41373990Full record

ReviewNutrients2025

Lipid Metabolism-Signaling Crosstalk in Metabolic Disease and Aging: Mechanisms and Therapeutic Targets.

Paalki Sethi, Awdhesh Kumar Mishra, Shampa Ghosh, Krishna Kumar Singh, Samarth Sharma, Radoslav Stojchevski, Dimiter Avtanski, Jitendra Kumar Sinha

Abstract readReview
In one paragraph

Review in Nutrients, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed, 1 pooled it
field-weighted citation impact
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

13 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Review
  13. Article
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

8 authors.

Paalki SethiGloNeuro, Sector 107, Vishwakarma Road, Noida 201301, India.ORCID 0009-0005-6062-475X
Awdhesh Kumar MishraDepartment of Biotechnology, Yeungnam University, Gyeongsan 38541, Republic of Korea.ORCID 0000-0002-3312-3264
Shampa GhoshGloNeuro, Sector 107, Vishwakarma Road, Noida 201301, India.ORCID 0000-0002-3252-7216
Krishna Kumar SinghSymbiosis Centre for Information Technology (SCIT), Symbiosis International (Deemed University), Rajiv Gandhi InfoTech Park, Hinjawadi, Pune 411057, India.ORCID 0000-0003-3849-5945
Samarth SharmaGL Bajaj Institute of Technology and Management, Greater Noida 201308, India.ORCID 0000-0003-3176-4268
Radoslav StojchevskiFriedman Diabetes Institute, Lenox Hill Hospital, Northwell Health, New York, NY 10022, USA.ORCID 0000-0002-5942-1622
Dimiter AvtanskiFriedman Diabetes Institute, Lenox Hill Hospital, Northwell Health, New York, NY 10022, USA.ORCID 0000-0002-4479-6448
Jitendra Kumar SinhaGloNeuro, Sector 107, Vishwakarma Road, Noida 201301, India.ORCID 0000-0002-7444-6932

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Lipid metabolism and lipid-derived signaling together ensure cellular and systemic homeostasis. Their dysregulation causes obesity, type 2 diabetes, cardiovascular disease, NAFLD/MASH, and neurodegeneration throughout life. This review integrates central pathways, such as ACC-FASN-mediated de novo lipogenesis, lipid-droplet lipolysis, and mitochondrial and peroxisomal β-oxidation, and their regulation by insulin-PI3K-Akt, glucagon-cAMP-PKA, SREBPs, PPARs, and AMPK. We emphasize the mechanisms by which bioactive lipids like diacylglycerols, ceramides, eicosanoids, and endocannabinoids serve as second messengers linking nutrient state to insulin signaling, inflammation, and stress response; pathologic accumulation of these species enhances insulin resistance and lipotoxicity. Aging disrupts these axes via diminished catecholamine-stimulated lipolysis, defective fatty-acid oxidation, mitochondrial failure, and adipose depot redistribution, facilitating ectopic fat and postprandial dyslipidemia. We suggest a pathway-to-phenotype paradigm that connects lipid species and tissue environment to clinical phenotypes, allowing for mechanism-to-intervention alignment. Therapeutic avenues range from lipid lowering for atherogenic risk to novel agents targeting ACLY, ACC, FASN, CPT1, and nuclear receptors, with precision lifestyle intervention in diet and exercise. Translation is still heterogeneous because of isoform-dependent effects, safety trade-offs, and inconsistent adherence. We prioritize harmonization of lipidomics with multi-omics for stratifying patients, enriching responders, and bridging gaps between mechanistic understanding and clinical outcome, with focus on age-sensitive prevention and treatment for lipid-mediated metabolic disease.

Indexed as

AgingLipid MetabolismMetabolic DiseasesSignal TransductionAnimalsHumansagingbioactive lipidsinsulin resistancelipid metabolismlipotoxicityMASLD (formerly NAFLD)obesitytype 2 diabetes

Identifiers

PMID41373990
PMCPMC12693963

What Socratic 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 Socratic graph.