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Exploring the Nutrient Sensing Mechanisms and Metabolic Regulatory Networks of Metabolic Diseases

A special issue of Nutrients (ISSN 2072-6643). This special issue belongs to the section "Nutrition and Metabolism".

Deadline for manuscript submissions: 5 August 2026 | Viewed by 3448

Editor


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Guest Editor
Department of Pharmaceutical Sciences, University of Kentucky, Lexington, KY, USA
Interests: metabolic disease; glial physiology; glucose sensing; endozepines; type 2 diabetes; neuroscience; circumventricular organs; vagal communication

Special Issue Information

Dear Colleagues,

Accurate sensing of a surplus or deficit of energy is critical for metabolic health and elicits compensatory responses that promote homeostasis of both circulating and stored fuel. However, an individual’s ability to adapt to changes in the systemic energy level is affected in the presence of metabolic disease. Deficits in central and peripheral detection of nutrient state signals dysregulate long-term fuel storage and availability, but the mechanisms underlying this dysregulation require further exploration.

In this Special Issue, we welcome contributions that evaluate central and peripheral mechanisms of nutrient sensing and the downstream networks that mediate responses to dynamic energetic demands, both on cellular and systemic levels. Original research articles and focused reviews investigating the detection of nutrients or nutrient-responsive signals, the impact of these nutrient-sensing mechanisms on human health, and the consequence of their dysfunction in metabolic disease are encouraged. 

Dr. Caroline Geisler
Guest Editor

Manuscript Submission Information

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • glucose
  • lipids
  • ketones
  • bile acids
  • nutrient state
  • energy balance
  • metabolic disease
  • fuel homeostasis
  • obesity
  • fasting
  • liver
  • vagal nerve
  • brain–body/body–brain communication
  • hypothalamus
  • dorsal vagal complex

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Published Papers (2 papers)

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Review

29 pages, 2064 KB  
Review
Circadian Timekeeping Through Nutritional and Metabolic Sensory Networks
by Erin N. Doherty and Lauren N. Woodie
Nutrients 2026, 18(7), 1133; https://doi.org/10.3390/nu18071133 - 31 Mar 2026
Cited by 1 | Viewed by 2046
Abstract
Circadian rhythms are predictable biological patterns that recur about every 24 h and, in mammals such as humans, are entrained to daylight by the hypothalamic suprachiasmatic nucleus (SCN). Although light is a potent zeitgeber for the SCN, cells outside of the SCN can [...] Read more.
Circadian rhythms are predictable biological patterns that recur about every 24 h and, in mammals such as humans, are entrained to daylight by the hypothalamic suprachiasmatic nucleus (SCN). Although light is a potent zeitgeber for the SCN, cells outside of the SCN can synchronize to daily nutrient and metabolic cues. In these tissues, nutrient metabolic processes are regulated by the molecular clock in anticipation of food availability or scarcity. Furthermore, nutrients and metabolic processes themselves may act upon members of the molecular clock to regulate their expression and activity. These interactions maintain synchrony between the SCN and food-entrainable clocks when activity and nutrient intake align. However, the light-entrainable SCN and food-entrainable clocks can become desynchronized, particularly in modern society where humans are commonly exposed to shift work and jet lag. Therefore, the mechanisms for sensing nutrients at specific times of day are critical components of circadian timekeeping and organismal homeostasis. In the following narrative review, we aim to synthesize current evidence on time-of-day-dependent nutrient sensing in mammalian systems, examine how nutrient-derived signals and metabolic processes interact with molecular clock mechanisms across cellular and tissue levels, and evaluate the integration of central and peripheral clocks in regulating gene expression, energy utilization, and organismal homeostasis, including the impacts of feeding cycles and circadian disruption. While previous reviews have discussed circadian nutrient metabolism, this review provides conceptual support for the role of nutrients as time-of-day signaling mechanisms. Full article
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11 pages, 373 KB  
Review
Endothelial Cells as Active Lipid Gatekeepers: Vascular Control of Lipid Handling and Metabolic Homeostasis
by Takeshi Kanda and Hidonori Urai
Nutrients 2026, 18(7), 1095; https://doi.org/10.3390/nu18071095 - 29 Mar 2026
Viewed by 895
Abstract
Endothelial cells have emerged as critical peripheral nutrient sensors that actively regulate systemic lipid metabolism rather than serving as passive conduits. Endothelial peroxisome proliferator-activated receptor γ maintains redox balance, supports nitric oxide-dependent perfusion, and preserves insulin sensitivity during high-fat feeding, while ghrelin signaling [...] Read more.
Endothelial cells have emerged as critical peripheral nutrient sensors that actively regulate systemic lipid metabolism rather than serving as passive conduits. Endothelial peroxisome proliferator-activated receptor γ maintains redox balance, supports nitric oxide-dependent perfusion, and preserves insulin sensitivity during high-fat feeding, while ghrelin signaling through endothelial GHS-R promotes triglyceride clearance and lipid uptake into white adipose tissue through an endothelial peroxisome proliferator-activated receptor γ-dependent program. These pathways reveal that the endothelium integrates hormonal and metabolic cues to tune lipid trafficking, vectorial fatty acid delivery, and depot-specific energy storage. The concept that the endothelial phenotype, rather than circulating lipid levels alone, determines organ-level lipid exposure reframes endothelial lipid sensing as a key regulator of whole-body metabolic homeostasis. Understanding how endocrine and transcriptional pathways shape endothelial lipid handling may reveal new therapeutic targets for the treatment of obesity, dyslipidemia, and related metabolic diseases. Full article
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