Open research questions in Regulation of Appetite and Obesity
134 unresolved questions extracted from the limitations and future-work sections of 447 Regulation of Appetite and Obesity papers in our library. Each links back to the study that raised it.
What the literature leaves open
Investigating the peripheral effects of SCFAs, - Studying the long-term effects of central SCFA administration on feed intake and gene expression, - Examining the effects of different doses and combinations of SCFAs
Short-chain fatty acids differentially regulate feed intake and hypothalamic appetite-related genes in layer-type chicks · 2026 · DOIThe study faces the challenge of developing a new therapeutic approach for the treatment of obesity and diabetes. The paper must overcome the limitations and adverse effects of current treatments. The study needs to understand the molecular mechanisms underlying metabolic disorders and the effects of the BAMLET complex on these mechanisms.
Balancing metabolism–control of weight gain, blood glucose levels and intestinal leakiness by alpha-lactalbumin-oleic acid complexes · 2026 · DOIInvestigation of the biodistribution of BAMLET, - Comparison of the intestinal retention of BAMLET in different mouse models, - Further study of the therapeutic potential of BAMLET
Balancing metabolism–control of weight gain, blood glucose levels and intestinal leakiness by alpha-lactalbumin-oleic acid complexes · 2026 · DOIThe available literature on NPY and autophagy in brain ageing is limited and methodologically heterogeneous, - The distinction between brain ageing itself and disease-specific neurodegeneration, - The complexity of ageing as a biological process
The available literature on NPY and autophagy in brain ageing is limited and methodologically heterogeneous, - The review only included studies published between 2014 and 2026, - The review excluded studies on defined neurodegenerative diseases or acute neurological insults
The use of GLP-1-based drugs comes with dose-dependent adverse effects, - Many patients struggle to reach their glycaemic and weight loss targets, - The mechanisms by which GIP regulates energy balance remain controversial
Understanding the mechanisms by which GIP engages brain circuits to reduce food intake and body weight, - Investigating the therapeutic potential of targeting GIP receptors (GIPR), - Elucidating the role of GIPR signalling in the CNS
Hunger enhances the motivational value of food, but the neural circuits linking homeostatic hunger neurons to dopamine systems remain poorly understood.
Although higher protein intake alters multiple metabolic responses, the exact neuro-metabolic mechanisms underlying food craving remain unclear.
However, these factors have rarely been considered together in humans, and thus their relative contributions to cognition remain unclear.
Adiposity, diet or inactivity – which is the culprit in obesity-related memory deficits in human adults? · 2026 · DOILactate, a metabolic product of high-intensity training, may possess exercise-mimicking effects that promote fat loss via the hypothalamic-adipose axis, yet its neuronal targets remain unclear.
Exercise-mimicking effect of exogenous lactate administration: Promoting visceral fat reduction via ventromedial hypothalamic SF-1 neurons in female rats · 2026 · DOIHowever, the mechanisms coupling weight gain and lipid metabolism are poorly understood.
Obesity due to MC4R deficiency is associated with reduced cholesterol, triglycerides and cardiovascular disease risk · 2025 · DOIHowever, high-fat diets are typically provided freely to animals in obesity experiments, so it remains unclear whether high-fat diets would still cause obesity if these diets required more effort to obtain.
However, the association of these two polymorphisms with GDM in Chinese remains unknown.
GLIS3 rs7034200 and ADRB3 rs4994 genetic variants associated with an increased risk of gestational diabetes mellitus in Chinese women: a case-control study · 2025 · DOILeptin has been suggested to play a role in modulating the inflammatory response in sepsis and improving outcomes; however, there are conflicting results regarding the outcome of sepsis.
Future research should explore leptin's role in IL-6-mediated inflammation and its potential protective effect in high IL-6 sepsis cases.
Conclusion In conclusion, these results will assist in the further investigation of the molecular mechanisms in which MC3R and MC4R were involved in the regulation of energy homeostasis in fish.
Cloning, distribution, and effects of growth regulation of MC3R and MC4R in red crucian carp (Carassius auratus red var.) · 2024 · DOIThe contribution of astrocytes located in the lateral parabrachial nucleus (lPBN) to feeding behavior control remains poorly understood.
Nevertheless, the mechanistic pathway linking plasma leptin and AD-related cognitive decline is not yet fully understood.
Triple receptor agonist retatrutide (GLP-1/GIP/glucagon receptor) demonstrates superior metabolic efficacy compared to dual agonists, but preclinical neuroprotective and anti-inflammatory effects remain preliminary and unvalidated in clinical populations. Studies must determine whether retatrutide modulates central inflammatory and neuroimmune pathways through GLP-1 and GIP receptor engagement in appetite-regulating brain regions.
The direct effects of lifestyle interventions and incretin-based therapies (GLP-1 receptor agonists, dual GLP-1/GIP agonists) on brain inflammation and blood-brain barrier integrity remain poorly characterized. Clinical validation studies are needed to determine whether these metabolic improvements translate to measurable reductions in central neuroinflammation and barrier dysfunction.
The role of vagal sensory nerves in thermoregulation remains poorly understood - The underlying autonomic reflex pathways involved in CCK-8-induced thermogenesis are not well characterized
Peripheral cholecystokinin promotes thermogenesis via vagal afferent signalling, hypothalamic oxytocin and sympathetic outflow to brown adipose tissue · 2026 · DOIAlthough exogenous CCK has been reported to induce thermogenesis in intrascapular brown adipose tissue (iBAT), whether this effect depends on vagal pathways and specific central circuits remains incompletely understood.
Peripheral cholecystokinin promotes thermogenesis via vagal afferent signalling, hypothalamic oxytocin and sympathetic outflow to brown adipose tissue · 2026 · DOIFurther studies are needed to investigate the long-term effects of the 5:2 diet. The study's findings suggest that the activation of GHSR may be a key mechanism of action of the 5:2 diet, and further studies are needed to investigate this mechanism. The study's findings may inform the development of new weight loss interventions that target the activation of GHSR.
The 5:2 diet induces male-specific weight loss and sex-independent enhancement of lipid storage in mice via activation of GHSR · 2026 · DOIThere is a gap in the understanding of the relationship between the preptin-myostatin axis and glycemic control, insulin resistance, inflammation, and atherogenic risk in patients with type 2 diabetes mellitus. The study aims to fill this gap by examining the changes in the preptin-myostatin axis and their association with glycemic control and atherogenic risk.
Alterations of the preptin–myostatin axis and their association with glycemic control and atherogenic risk in type 2 diabetes mellitus · 2026 · DOI
Most-cited papers in Regulation of Appetite and Obesity
- Central nervous system control of food intake · Nature · 2000 · 4,748 citations
- Serum Immunoreactive-Leptin Concentrations in Normal-Weight and Obese Humans · New England Journal of Medicine · 1996 · 4,639 citations
- Genetic studies of body mass index yield new insights for obesity biology · Nature · 2015 · 4,292 citations
- Leptin and the regulation of body weight in mammals · Nature · 1998 · 4,077 citations
- The hormone resistin links obesity to diabetes · Nature · 2001 · 3,594 citations
- Weight-Reducing Effects of the Plasma Protein Encoded by the obese Gene · Science · 1995 · 3,407 citations
- Ghrelin induces adiposity in rodents · Nature · 2000 · 3,099 citations
- Effects of the obese Gene Product on Body Weight Regulation in ob / ob Mice · Science · 1995 · 3,089 citations
- A role for ghrelin in the central regulation of feeding · Nature · 2001 · 2,697 citations
- Extending Healthy Life Span—From Yeast to Humans · Science · 2010 · 2,648 citations
Most recent work
- Current and Future Pharmacological Interventions for Acquired Hypothalamic Obesity · Drugs · 2026
- A selective and augmentable butyrate-FFAR2 signal circuitry programs the cellular identity of enteroendocrine L-cells · Communications Biology · 2026
- Direct interoceptive input to the insular cortex shapes learned feeding behavior · bioRxiv · 2026
- WNKs regulate mouse behavior and alter central nervous system glucose uptake and insulin signaling · bioRxiv · 2026
- A skin-hypothalamus axis couples heat stress and metabolic dysfunction · Cell · 2026
- Insulin in brain: The physiological functions and therapeutic insights for neurodegenerative diseases · Life Sciences · 2026
- A cross-species atlas of the dorsal vagal complex reveals neural mediators of the effects of cagrilintide on energy balance · Nature Metabolism · 2026
- Distinct brain regions mediate regulation of food intake in response to GIPR agonism or antagonism · Nature Metabolism · 2026
- Multidimensional control of ingestive behavior by lateral hypothalamic neurotensin neurons · bioRxiv · 2026
- A central role for dietary sugars in human evolution · Science · 2026
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