Adiponectin, leptin and ghrelin: key hormonal players in feline diabetes mellitus and hypersomatotropism

11 March 2026

There are an estimated 39,000 cats with diabetes mellitus (DM) in the UK.1,2 DM in cats is the consequence of inadequate insulin production which typically occurs via a combination of insulin resistance and pancreatic β cell dysfunction.

Obesity and growth hormone excess (hypersomatotropism) can contribute to insulin resistance and are modifiable risk factors for feline DM. The mechanisms linking excessive adiposity with impaired glucose homeostasis and growth hormone excess with polyphagia (which often result in weight gain) remain incompletely understood. Adipose tissue-derived hormones (adipokines) and gut-derived peptides may contribute to the pathogenesis of these metabolic diseases.

Two important adipokines are adiponectin and leptin. Adiponectin is exclusively secreted by adipose tissue, and functions as an insulin sensitiser with anti-inflammatory properties. Leptin is also produced by adipocytes, and has a role in the regulation of satiety. Ghrelin is primarily synthesised in the stomach, stimulates appetite and influences insulin secretion and glucose homeostasis.

Adiponectin

Feline adiponectin has 89% and 84% homology to the canine and human adiponectin proteins, respectively. Adiponectin circulates in three distinct oligomeric forms: low molecular weight (LMW) trimers, medium molecular weight (MMW) hexamers, and high molecular weight (HMW) multimers. These different isoforms exhibit distinct biological activities, with HMW adiponectin being the most biologically active.

In contrast to most adipokines that increase in concentration with increasing adiposity, adiponectin concentrations paradoxically decrease in obesity.3,4 As adiponectin is an insulin sensitiser, this inverse relationship between adiposity and circulating adiponectin represents a critical pathophysiological link between obesity and insulin resistance.

Weight gain in cats is associated with a decrease in insulin sensitivity, with an estimated 30% decrease of insulin sensitivity with every 1kg gained in lean cats.5 There are inconsistent reports of the effect of weight loss and serum adiponectin, with one study which measured serum adiponectin after a 6 month weight loss programme reporting a decrease in adiponectin, and another finding no significant difference from baseline when monitoring cats during a 9 week programme of weight loss.5,6 These findings suggest that adiponectin normalisation may take time to become apparent following weight loss, and therefore some of the benefits of weight loss on glycaemic control may be delayed.

Male cats have a higher risk of DM compared to females, and adiponectin may partially explain this sex-based disparity.2 Neutered male cats have been reported to have lower blood adiponectin in some but not all studies, and in the studies reporting a difference, this persisted after controlling for body fat percentage, fat mass, and lean body mass.3,7,8 Lower adiponectin concentrations may contribute to the increased risk of DM in lean male cats compared to females, a risk that is further exacerbated by even lower adiponectin concentrations in obesity.9

Leptin

Leptin is the product of the obese (ob) gene, which acts as a satiety hormone and increases energy expenditure. In cats, plasma leptin concentrations strongly correlate with fat mass.10,11 Leptin could be considered an ‘adipostat’ as it provides feedback to the central nervous system about the amount of white fat in the body, with subsequent regulation of food intake and energy use. However, despite the increased leptin concentrations observed previously in obese cats, these cats continued to consume excessive calories and demonstrated a state of leptin resistance.10 This resistance to leptin’s satiety effects represents a key defect in obesity pathophysiology in cats as well as other species.

Leptin may also have a significant interaction with glycaemic control. Increased leptin has been associated with insulin resistance in lean and overweight cats, with leptin concentrations reported to be higher in newly diagnosed diabetic cats compared to healthy controls, and in cats which had achieved diabetic remission compared to healthy controls.9,12,13 However, leptin concentrations did not correlate with increasing insulin resistance in four obese male cats followed over a 4 year period.14 Therefore, there may be inter-individual variability of leptin concentrations, and other factors beyond obesity and insulin resistance may contribute to a particular individual’s leptin concentration.

Ghrelin

Ghrelin is a peptide hormone primarily synthesised by gastric oxyntic cells, and is the classic peripherally-produced orexigenic (appetite stimulating) hormone. It circulates as acylated and des-acylated fractions, which have differing metabolic effects. Ghrelin is released in response to fasting and suppressed following food intake, and stimulates appetite. This effect has clinical applications in veterinary practice with capromorelin, a ghrelin mimic, being used as a treatment for inappetence in dogs (Entyce, Elanco) and cats (Elura, Elanco).15

Ghrelin also has a role in glycaemic control. Acyl-ghrelin directly suppressed glucose-induced insulin release from pancreatic beta cells in a rodent model and indirectly caused insulin resistance by increasing growth hormone secretion, whilst des-acyl-ghrelin acts as an insulin sensitiser.16,17

In contrast to humans, obese cats were reported to have increased acyl-ghrelin concentrations.18,19 This was associated with increased energy intake per kg fat-free mass in obese compared to lean cats, despite similar absolute food intake. Acyl-ghrelin concentrations also remained increased for at least 100 minutes post-prandially regardless of dietary composition in these obese cats, again conflicting with the post-prandial decline observed in humans.20 Conversely, acyl-ghrelin levels were decreased in cats with diabetes compared to healthy cats in one study, so the physiology of acyl-ghrelin appears to be altered after the onset of DM. Whether this represents a physiological adaptation to decrease further insulin resistance is unknown. Alterations of desacyl-ghrelin are yet to be described in cats with obesity or DM, but would be useful to know as this hormone could be considered a useful therapeutic insulin sensitiser.

Another poorly understood phenomenon is the polyphagia which occurs in hypersomatotropism / acromegaly and which can persist following hypophysectomy despite the resolution of growth hormone excess and DM. Polyphagia affects the quality of life of cats with hypersomatotropism and their owners, with some owners reporting they are no longer able to eat in the same room as their cat, and the need to put child locks on their cupboards. Although the proportion of cats with hypersomatotropism is small, the condition is still estimated to affect nearly 10,000 cats in the UK.21 Moreover, while there is some evidence that ghrelin concentrations are decreased in cats with hypersomatotropism and DM, and increased following pituitary radiotherapy.22 the effect of the complete resolution of hypersomatotropism has not been described.

The research question: looking at the effect of hypophysectomy on key hormones regulating appetite, metabolism and body weight

With thanks to funding from BSAVA PetSavers and SamSoc, we are currently studying the effect of hypophysectomy on leptin, adiponectin and ghrelin concentrations in cats. As hypophysectomy is typically associated with the resolution of hypersomatotropism and DM, exploring the impact of the return to a more physiologically normal state on leptin, adiponectin and ghrelin may help to explain why some cats continue to have an increased appetite post-surgery. We hope to measure these hormones pre- and post-hypophysectomy in 10 cats using residual serum from clinical samples which have been stored in our biobank, and which owners have consented for use in research.

A challenge we have faced this year has been the unavailability of DDAVP nasal spray since March 2025. This has been a nationwide shortage which has also impacted human healthcare. As all cats have an absolute requirement for arginine vasopressin supplementation in the immediate post-hypophysectomy period and we did not wish to orally pill cats which had recently undergone soft palate surgery, we elected to temporarily postpone our hypophysectomy service until this drug became available again rather than prescribe oral desmopressin in the first week post-hypophysectomy. We are very pleased to report that we can now obtain DDAVP nasal spray once again and have re-opened our hypophysectomy service for both cats and dogs. If you have a patient who you believe may be a suitable candidate for this procedure, please contact us via QMHreception@rvc.ac.uk for the attention of Christopher Scudder and Joe Fenn.

Conclusion

Adiponectin, leptin, and ghrelin do not function in isolation but are part of an integrated hormonal network regulating appetite, energy balance and glucose homeostasis. For example, ghrelin stimulates neuropeptide Y and Agouti-related peptide which increase appetite, whilst leptin inhibits them. As we gradually understand the role of these hormones in appetite, obesity and diabetes pathogenesis, we may reach a state whereby we can recognise individuals at risk of diabetes, identify potential future therapeutics, and make management changes or use existing therapeutics which decrease the likelihood of these metabolic conditions.

About the author

Chris graduated from the University of Bristol, then worked in private practice for several years before undertaking a rotating internship at the University of Bristol. He then completed an internal medicine residency followed by a PhD at the Royal Veterinary College where he now works as a senior lecturer in small animal internal medicine.

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