ArticleNature medicine2011
Brain PPAR-γ promotes obesity and is required for the insulin-sensitizing effect of thiazolidinediones.
Article in Nature medicine, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 137 papers.
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Who cites it
137 citing papers in PubMed, 228 citations in OpenAlex.
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- The role of PPARγ in cancer cachexia: friend or foe?Frontiers in endocrinology · 2025Review
- New advances in drug development for metabolic dysfunction-associated diseases and alcohol-associated liver disease.Cell & bioscience · 2024Review
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- Highlights from the Top 100 Most Influential Articles Regarding the Nuclear Receptor PPAR-γ: A Bibliometric Analysis.Endocrine, metabolic & immune disorders drug targets · 2024Article
- Immune dysregulation and macrophage polarization in peri-implantitis.Frontiers in bioengineering and biotechnology · 2024Review
- Identification of Crocetin as a Dual Agonist of GPR40 and GPR120 Responsible for the Antidiabetic Effect of Saffron.Nutrients · 2023Article
- Assessing the multitargeted antidiabetic potential of three pomegranate peel-specific metabolites: An in silico and pharmacokinetics study.Food science & nutrition · 2023Article
- PPAR-γ activation promotes xenogenic bioroot regeneration by attenuating the xenograft induced-oxidative stress.International journal of oral science · 2023Article
- Regulatory T cells differentiation in visceral adipose tissues contributes to insulin resistance by regulating JAZF-1/PPAR-γ pathway.Journal of cellular and molecular medicine · 2023Article
- Brain nuclear receptors and cardiovascular function.Cell & bioscience · 2023Review
- The rheumatoid arthritis drug auranofin lowers leptin levels and exerts antidiabetic effects in obese mice.Cell metabolism · 2022Article
- The contribution of astrocytes to obesity-associated metabolic disturbances.Journal of biomedical research · 2022Article
- The Small Molecule PPARγ Agonist GL516 Induces Feeding-Stimulatory Effects in Hypothalamus Cells Hypo-E22 and Isolated Hypothalami.Molecules (Basel, Switzerland) · 2022Article
- Implications of peroxisome proliferator-activated receptor gamma (PPARY) with the intersection of organophosphate flame retardants and diet-induced obesity in adult mice.Journal of toxicology and environmental health. Part A · 2022Article
- Isoform-specific functions of PPARγ in gene regulation and metabolism.Genes & development · 2022Article
- Rosiglitazone Requires Hepatocyte PPARγ Expression to Promote Steatosis in Male Mice With Diet-Induced Obesity.Endocrinology · 2021Article
- Key Disease Mechanisms Linked to Alzheimer's Disease in the Entorhinal Cortex.International journal of molecular sciences · 2021Article
- Role of the Peroxisome Proliferator Activated Receptors in Hypertension.Circulation research · 2021Review
77 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
In adipose tissue, muscle, liver and macrophages, signaling by the nuclear receptor peroxisome proliferator-activated receptor-γ (PPAR-γ) is a determinant of insulin sensitivity and this receptor mediates the insulin-sensitizing effects of thiazolidinediones (TZDs). As PPAR-γ is also expressed in neurons, we generated mice with neuron-specific Pparg knockout (Pparg brain knockout (BKO)) to determine whether neuronal PPAR-γ signaling contributes to either weight gain or insulin sensitivity. During high-fat diet (HFD) feeding, food intake was reduced and energy expenditure increased in Pparg-BKO mice compared to Pparg(f/f) mice, resulting in reduced weight gain. Pparg-BKO mice also responded better to leptin administration than Pparg(f/f) mice. When treated with the TZD rosiglitazone, Pparg-BKO mice were resistant to rosiglitazone-induced hyperphagia and weight gain and, relative to rosiglitazone-treated Pparg(f/f) mice, experienced only a marginal improvement in glucose metabolism. Hyperinsulinemic euglycemic clamp studies showed that the increase in hepatic insulin sensitivity induced by rosiglitazone treatment during HFD feeding was completely abolished in Pparg-BKO mice, an effect associated with the failure of rosiglitazone to improve liver insulin receptor signal transduction. We conclude that excess weight gain induced by HFD feeding depends in part on the effect of neuronal PPAR-γ signaling to limit thermogenesis and increase food intake. Neuronal PPAR-γ signaling is also required for the hepatic insulin sensitizing effects of TZDs.
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Registered trials
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.