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Regulation of Appetite and Obesity
Research Guide
What is Regulation of Appetite and Obesity?
Regulation of Appetite and Obesity is the neuroendocrine control of food intake and body weight through hormones such as leptin, ghrelin, and insulin, involving hypothalamic neural circuits that maintain energy balance and metabolic homeostasis.
This field examines 72,101 papers on how leptin, ghrelin, and insulin modulate feeding behavior via the hypothalamus and melanocortin system. Central nervous system circuits integrate these hormonal signals to regulate energy balance, as detailed in foundational works. Obese individuals often show elevated leptin levels yet remain insensitive to its effects, linking hormonal dysregulation to weight gain.
Topic Hierarchy
Research Sub-Topics
Leptin Signaling Pathways
Leptin signaling pathways research investigates the molecular mechanisms of leptin action in the hypothalamus and periphery. Researchers study receptor isoforms, downstream JAK-STAT signaling, and resistance mechanisms in obesity.
Ghrelin Receptor Physiology
Ghrelin receptor physiology examines the GHS-R1a receptor's role in appetite stimulation and growth hormone release. Researchers explore acylation requirements, heterodimerization, and inverse agonist development.
Hypothalamic Neural Circuits Feeding
This subfield maps neural circuits in the arcuate, paraventricular, and lateral hypothalamus regulating food intake. Researchers use optogenetics and chemogenetics to dissect orexigenic and anorexigenic pathways.
Melanocortin System Obesity
Melanocortin system research focuses on MC3R and MC4R receptors in energy homeostasis and their mutations in monogenic obesity. Researchers investigate agonist development and downstream effectors like SIM1.
Adipokine Dysregulation Metabolic Syndrome
Adipokine dysregulation studies adiponectin, resistin, and visfatin roles in insulin resistance and inflammation. Researchers analyze adipose tissue secretome changes and therapeutic restoration strategies.
Why It Matters
Understanding appetite regulation addresses obesity's role in metabolic syndrome, where fat accumulation elevates systemic oxidative stress, as Furukawa et al. (2004) demonstrated in humans and mice with correlations between adipose oxidative stress and insulin resistance. Leptin resistance in obese humans, with serum concentrations correlating to body fat percentage (Considine et al., 1996), underlies failed satiety signaling and overeating. Ghrelin from the stomach stimulates growth hormone release and appetite (Kojima et al., 1999), while adiponectin levels paradoxically drop in obesity despite insulin resistance (Arita et al., 1999), offering targets for therapies; resistin links obesity to diabetes by impairing insulin action (Steppan et al., 2001). These mechanisms inform treatments in endocrine and autonomic systems, impacting over 500 million obese adults worldwide through disrupted energy homeostasis.
Reading Guide
Where to Start
"Central nervous system control of food intake" by Schwartz et al. (2000), as it provides a foundational overview of hypothalamic integration of leptin, insulin, and other signals for energy balance, accessible before diving into specific hormones.
Key Papers Explained
"Ghrelin is a growth-hormone-releasing acylated peptide from stomach" by Kojima et al. (1999) discovered the orexigenic stomach hormone, building the appetite stimulation side reviewed in "Central nervous system control of food intake" by Schwartz et al. (2000). This pairs with "Serum Immunoreactive-Leptin Concentrations in Normal-Weight and Obese Humans" by Considine et al. (1996), which established leptin resistance in obesity, and "Leptin and the regulation of body weight in mammals" by Friedman and Halaas (1998), detailing its anorexigenic role. "Orexins and Orexin Receptors: A Family of Hypothalamic Neuropeptides and G Protein-Coupled Receptors that Regulate Feeding Behavior" by Sakurai et al. (1998) extends neural circuit insights, while "Adipose Tissue as an Endocrine Organ" by Kershaw and Flier (2004) connects adipose hormones to hypothalamic control.
Paper Timeline
Most-cited paper highlighted in red. Papers ordered chronologically.
Advanced Directions
Current research builds on leptin resistance and oxidative stress in adipose tissue, as in Furukawa et al. (2004) and adiponectin paradoxes from Arita et al. (1999), focusing on therapeutic targeting of resistin pathways (Steppan et al., 2001). No recent preprints or news available, so frontiers remain in unresolved neural-hormonal interactions from top-cited works.
Papers at a Glance
| # | Paper | Year | Venue | Citations | Open Access |
|---|---|---|---|---|---|
| 1 | Ghrelin is a growth-hormone-releasing acylated peptide from st... | 1999 | Nature | 8.4K | ✕ |
| 2 | Central nervous system control of food intake | 2000 | Nature | 6.4K | ✕ |
| 3 | Serum Immunoreactive-Leptin Concentrations in Normal-Weight an... | 1996 | New England Journal of... | 6.3K | ✕ |
| 4 | Orexins and Orexin Receptors: A Family of Hypothalamic Neurope... | 1998 | Cell | 5.5K | ✓ |
| 5 | Adipose Tissue as an Endocrine Organ | 2004 | The Journal of Clinica... | 5.4K | ✓ |
| 6 | Leptin and the regulation of body weight in mammals | 1998 | Nature | 5.3K | ✕ |
| 7 | Increased oxidative stress in obesity and its impact on metabo... | 2004 | Journal of Clinical In... | 5.2K | ✓ |
| 8 | The fat-derived hormone adiponectin reverses insulin resistanc... | 2001 | Nature Medicine | 4.9K | ✕ |
| 9 | Paradoxical Decrease of an Adipose-Specific Protein, Adiponect... | 1999 | Biochemical and Biophy... | 4.8K | ✕ |
| 10 | The hormone resistin links obesity to diabetes | 2001 | Nature | 4.7K | ✕ |
Frequently Asked Questions
What is ghrelin and its role in appetite?
Ghrelin is a growth-hormone-releasing acylated peptide produced in the stomach. Kojima et al. (1999) identified it as a key regulator of feeding behavior. It stimulates appetite and food intake through hypothalamic actions.
How does leptin regulate body weight?
Leptin, produced by adipose tissue, signals satiety to the hypothalamus to suppress food intake and maintain body weight. Friedman and Halaas (1998) showed its central role in mammals' energy balance. Obese humans exhibit high leptin levels but insensitivity, leading to overeating (Considine et al., 1996).
What neural circuits control food intake?
Hypothalamic circuits integrate hormonal inputs like leptin, insulin, and ghrelin to regulate feeding. Schwartz et al. (2000) outlined central nervous system control of food intake via these pathways. The melanocortin system within the hypothalamus mediates energy balance.
Why is adiponectin decreased in obesity?
Adiponectin, an adipose-derived hormone, drops paradoxically in obesity despite increased fat mass. Arita et al. (1999) reported lower levels in obese subjects compared to lean controls. This decrease associates with insulin resistance and metabolic dysfunction.
How does adipose tissue function as an endocrine organ?
Adipose tissue secretes hormones like leptin and adiponectin beyond mere fat storage. Kershaw and Flier (2004) described it as a complex endocrine organ with stromovascular and immune cells. It responds to nutritional states to influence whole-body metabolism.
What links obesity to oxidative stress?
Obesity elevates oxidative stress in adipose tissue, contributing to metabolic syndrome. Furukawa et al. (2004) correlated fat accumulation with systemic oxidative stress in humans and mice. This stress impairs insulin signaling and promotes inflammation.
Open Research Questions
- ? How do interactions between ghrelin and leptin signaling in hypothalamic circuits adapt to chronic overnutrition in obesity?
- ? What mechanisms cause leptin resistance in obese individuals despite elevated serum levels?
- ? How does the orexin system integrate with melanocortin pathways to fine-tune feeding under varying energy states?
- ? Why does adiponectin production decrease in obesity, and how does this interact with insulin resistance?
- ? What role does resistin play in linking adipose inflammation to diabetes progression?
Recent Trends
The field encompasses 72,101 papers with sustained interest in leptin resistance (Considine et al., 1996; 6307 citations) and ghrelin discovery (Kojima et al., 1999; 8399 citations), but growth rate data over 5 years is unavailable.
High-impact works like Furukawa et al. on oxidative stress (5164 citations) highlight ongoing focus on obesity's metabolic complications.
2004No recent preprints or news in the last 6-12 months indicate steady rather than accelerating publication trends.
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