Dataset Information

Cell type-specific transcriptomics of hypothalamic energy-sensing neuron responses to weight-loss.

ABSTRACT: Molecular and cellular processes in neurons are critical for sensing and responding to energy deficit states, such as during weight-loss. Agouti related protein (AGRP)-expressing neurons are a key hypothalamic population that is activated during energy deficit and increases appetite and weight-gain. Cell type-specific transcriptomics can be used to identify pathways that counteract weight-loss, and here we report high-quality gene expression profiles of AGRP neurons from well-fed and food-deprived young adult mice. For comparison, we also analyzed Proopiomelanocortin (POMC)-expressing neurons, an intermingled population that suppresses appetite and body weight. We find that AGRP neurons are considerably more sensitive to energy deficit than POMC neurons. Furthermore, we identify cell type-specific pathways involving endoplasmic reticulum-stress, circadian signaling, ion channels, neuropeptides, and receptors. Combined with methods to validate and manipulate these pathways, this resource greatly expands molecular insight into neuronal regulation of body weight, and may be useful for devising therapeutic strategies for obesity and eating disorders.

SUBMITTER: Henry FE

PROVIDER: S-EPMC4595745 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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Publications

Cell type-specific transcriptomics of hypothalamic energy-sensing neuron responses to weight-loss.

Henry Fredrick E FE Sugino Ken K Tozer Adam A Branco Tiago T Sternson Scott M SM

eLife 20150902

Molecular and cellular processes in neurons are critical for sensing and responding to energy deficit states, such as during weight-loss. Agouti related protein (AGRP)-expressing neurons are a key hypothalamic population that is activated during energy deficit and increases appetite and weight-gain. Cell type-specific transcriptomics can be used to identify pathways that counteract weight-loss, and here we report high-quality gene expression profiles of AGRP neurons from well-fed and food-depriv ...[more]

PMID: 26329458

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Project description:Research shows a positive relationship between dietary energy density (ED) and body mass index (BMI), but dietary ED of weight loss maintainers is unknown. This preliminary investigation was a secondary data analysis that compared self-reported dietary ED and food group servings consumed in overweight adults (OW: BMI=27-45kg/m(2)), normal weight adults (NW: BMI=19-24.9 kg/m(2)), and weight loss maintainers (WLM: current BMI=19-24.9kg/m(2) [lost?10% of maximum body weight and maintained loss for ?5years]) participating in 2 studies, with data collected from July 2006 to March 2007. Three 24-h phone dietary recalls from 287 participants (OW=97, NW=85, WLM=105) assessed self-reported dietary intake. ED (kcal/g) was calculated by three methods (food+all beverages except water [F+AB], food+caloric beverages [F+CB], and food only [FO]). Differences in self-reported consumption of dietary ED, food group servings, energy, grams of food/beverages, fat, and fiber were assessed using one-way MANCOVA, adjusting for age, sex, and weekly energy expenditure from self-reported physical activity. ED, calculated by all three methods, was significantly lower in WLM than in NW or OW (FO: WLM=1.39±0.45kcal/g; NW=1.60±0.43 kcal/g; OW=1.83±0.42 kcal/g). Self-reported daily servings of vegetables and whole grains consumed were significantly higher in WLM compared to NW and OW (vegetables: WLM=4.9±3.1 servings/day; NW=3.9±2.0 servings/day; OW=3.4±1.7 servings/day; whole grains: WLM=2.2±1.8 servings/day; NW=1.4±1.2 servings/day; OW=1.3±1.3 servings/day). WLM self-reported consuming significantly less energy from fat and more fiber than the other two groups. Self-reported energy intake per day was significantly lower in WLM than OW, and WLM self-reported consuming significantly more grams of food/beverages per day than OW. These preliminary findings suggest that consuming a diet lower in ED, characterized by greater intake of vegetables and whole grains, may aid with weight loss maintenance and should be further tested in prospective randomized controlled trials.

Dataset Information

Cell type-specific transcriptomics of hypothalamic energy-sensing neuron responses to weight-loss.

Publications

Cell type-specific transcriptomics of hypothalamic energy-sensing neuron responses to weight-loss.

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