Skip to content

Study · Animal study (in vivo) · rat · 2015

2 results

Defense of Elevated Body Weight Setpoint in Diet-Induced Obese Rats on Low Energy Diet Is Mediated by Loss of Melanocortin Sensitivity in the Paraventricular Hypothalamic Nucleus.

Luchtman DW, Chee MJ, Doslikova B, Marks DL, Baracos VE, Colmers WF

PloS one7 Oct 2015Cited by 6 (Europe PMC)

PMID26444289 (opens in a new tab)PMCIDPMC4596859 (opens in a new tab)DOI10.1371/journal.pone.0139462 (opens in a new tab)PepBankPUB-26444289
Download PDFPubMedAsk about this study
Jump to 2 results

Summary

Some animals and humans fed a high-energy diet (HED) are diet-resistant (DR), remaining as lean as individuals who were naïve to HED. Other individuals become obese during HED exposure and subsequently defend the obese weight (Diet-Induced Obesity- Defenders, DIO-D) even when subsequently maintained on a low-energy diet. We hypothesized that the body weight setpoint of the DIO-D phenotype resides in the hypothalamic paraventricular nucleus (PVN), where anorexigenic melanocortins, including melanotan II (MTII), increase presynaptic GABA release, and the orexigenic neuropeptide Y (NPY) inhibits it. After prolonged return to low-energy diet, GABA inputs to PVN neurons from DIO-D rats exhibited highly attenuated responses to MTII compared with those from DR and HED-naïve rats. In DIO-D rats, melanocortin-4 receptor expression was significantly reduced in dorsomedial hypothalamus, a major source of GABA input to PVN. Unlike melanocortin responses, NPY actions in PVN of DIO-D rats were unchanged, but were reduced in neurons of the ventromedial hypothalamic nucleus; in PVN of DR rats, NPY responses were paradoxically increased. MTII-sensitivity was restored in DIO-D rats by several weeks' refeeding with HED. The loss of melanocortin sensitivity restricted to PVN of DIO-D animals, and its restoration upon prolonged refeeding with HED suggest that their melanocortin systems retain the ability to up- and downregulate around their elevated body weight setpoint in response to longer-term changes in dietary energy density. These properties are consistent with a mechanism of body weight setpoint.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study2

2 results from studies that gave the peptide. No result from this study comes from people.

  1. 01AnimalAnimal study (in vivo)Mechanism

    After prolonged return to a low-energy diet, GABA inputs to PVN neurons from diet-induced-obese defender rats responded much less to MTII than those from diet-resistant and high-energy-diet-naive rats.

    In plain wordsIn rats that defend an obese body weight, nerve inputs in a brain area responded much less to melanotan II than in lean rats.

    Peptide
    Melanotan II
    Outcome
    DecreaseResponse of GABA inputs to PVN neurons to MTII in DIO-D rats
    Study

    ratn: not reported in source

    Comparator
    DR and HED-naive rats
    Outcome group
    Receptor activity and mechanism · Nervous system and cognition
    Studied dose
    Dose not stated

    Source sentences

    Summary
    After prolonged return to low-energy diet, GABA inputs to PVN neurons from DIO-D rats exhibited highly attenuated responses to MTII compared with those from DR and HED-naïve rats.
  2. 02AnimalAnimal study (in vivo)Mechanism

    In diet-induced-obese defender rats, several weeks of refeeding with a high-energy diet restored MTII sensitivity.

    In plain wordsIn rats that defend an obese weight, several weeks back on a high-energy diet restored their response to melanotan II.

    Peptide
    Melanotan II
    Outcome
    IncreaseRestoration of MTII sensitivity in DIO-D rats after HED refeeding
    Study

    ratn: not reported in source

    Comparator
    DIO-D rats before refeeding
    Outcome group
    Receptor activity and mechanism · Nervous system and cognition
    Studied dose
    Dose not stated

    Source sentences

    Summary
    MTII-sensitivity was restored in DIO-D rats by several weeks' refeeding with HED.

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 2Current

    10 Oct 2026, 09:43 UTC

    Study results updated

  2. Version 1

    9 Oct 2026, 03:04 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

PepBank is a research reference. Talk to a doctor before you use any peptide.