The increased risk of diabetes mellitus is one of the most serious effects of obesity. Chronically high blood glucose levels are the result of insulin resistance, which is caused by excess body fat and impairs the body’s ability to respond to insulin (Hoelmkjaer et al., 2016). Research shows that cats who are obese are far more likely to develop type 2 diabetes, and their insulin sensitivity decreases by 30% for every kilogram of body weight (Kocabağlı et al., 2017; Clark and Hoenig, 2021). These animals’ metabolic dysfunction is characterized by a combination of insulin resistance and glucotoxicity, which, if left untreated, can result in serious diabetes consequences (Lewitt et al., 2016; Clark and Hoenig, 2021; Martin and Wood, 2010).

Many studies have shown that overweight cats have higher fasting insulin levels, implying this issue (Vitor et al., 2024; Appleton et al., 2000b; Zapata et al., 2017; Hoelmkjaer et al., 2016). As a result, these cats could struggle to keep appropriate glucose homeostasis, which could influence their diabetes mellitus risk, a condition defined by consistently elevated blood sugar levels caused by insulin resistance. Recent research has revealed the processes behind the link between obesity and insulin resistance, especially in cats. For instance, Hoenig et al. found that, particularly in older populations, overweight cats show significant changes in postprandial glucose metabolism and decreased insulin sensitivity (Hoenig et al., 2011a). This is corroborated by Vitor et al., who found that in obese cats, higher blood glucose levels are correlated with higher body condition scores (Vitor et al., 2024; Lewitt et al., 2016). The dysregulation of glucose metabolism is exacerbated by changes in the secretion of adipokines, such as leptin and adiponectin, which are implicated in insulin signaling (Araújo et al., 2024; Takashima et al., 2016).

This interaction highlights how complicated cat metabolism is, especially when it comes to obesity and food composition. Being genuine carnivores, cats naturally consume a diet low in carbs and rich in protein. Due to unnatural nutritional constraints, insulin dynamics may be negatively altered by diets high in carbs, which can result in a reduction in insulin sensitivity (Brearley et al., 2006; Hoenig et al., 2007).

Furthermore, liver illness, especially hepatic lipidosis, which can happen when excessive fat buildup overtakes liver function, is closely associated with obesity in cats (Tarkošová et al., 2016). Because the liver cannot process fat effectively, fat increases and causes hepatic dysfunction, this condition is significantly more common in overweight and obese cats. Liver disease can have serious effects, including increased death rates and multi-organ dysfunction in cats (Tarkošová et al., 2016; Bjørnvad and Hoelmkjaer, 2014).

Reduced mobility and joint issues are also associated with obesity. Cats who are overweight are more likely to develop degenerative joint disease and lameness because of the increased stress on their joints (Maniaki et al., 2021; Bjørnvad and Hoelmkjaer, 2014). This disease is particularly worrisome since it produces persistent pain as well as decreases a cat’s activity level, hence aggravating obesity by decreasing exercise (Bjørnvad and Hoelmkjaer, 2014). Additionally, because obesity alters body composition and fat distribution, research has suggested a potential link between obesity and a higher prevalence of dermatological conditions and lower urinary tract issues (Tarkošová et al., 2016).

Leptin is a vital adipokine that is mostly secreted by adipose tissue and is necessary for regulating energy balance, metabolism, and appetite (Lee et al., 2007). It is essential for maintaining body weight homeostasis, and it is more prevalent in obese individuals, including cats (Takashima et al., 2016). Because it informs the hypothalamus about the condition of energy storage, leptin plays a crucial role in reducing appetite and raising energy expenditure (Zhao et al., 2019).

Because of the expansion of fat tissue, leptin levels usually increase when a cat is obese; it has also been shown to be positively related with body weight, body condition score, and body fat percentage (Vester et al., 2011). These relationships show leptin’s dual role as metabolic control and a sign of obesity. According to one study, overweight cats have greater leptin levels and acquire a kind of leptin resistance comparable to that seen in overweight humans (Lee et al., 2007; Appleton et al., 2000b). Hyperleptinemia is a condition in which high amounts of circulating leptin do not sufficiently control weight or decrease hunger (Sharma and Sharma, 2018). Apart from its connection to energy metabolism, leptin exhibits pro-inflammatory properties that may aggravate chronic inflammation caused by obesity (Booth et al., 2016; Araújo et al., 2024). Increased production of pro-inflammatory cytokines by macrophages and other immune cells infiltrating adipose tissue in obese individuals can worsen insulin resistance and metabolic dysfunction (Araújo et al., 2024). Furthermore, because of its interactions with other hormonal pathways, particularly its role in controlling insulin sensitivity, leptin is seen as a key factor in the evolution of obesity-related comorbidities such diabetes mellitus (Takashima et al., 2016).

Adiponectin is an important adipokine that regulates insulin sensitivity and metabolic health. It also has a big impact on feline obesity. Adiponectin, which is mostly secreted by adipose tissue, comes in a variety of forms (Frank and Walsh, 2017; Hoenig et al., 2011a; Takashima et al., 2016).

Studies revealing that adiponectin levels directly correlate with metabolic health in lean cats and obese cats have far lower circulating levels of adiponectin than cats with a lower body condition score (Tvarijonaviciute et al., 2012; Öhlund et al., 2015; Hoenig et al., 2013). Insulin resistance, a risk factor for diabetes mellitus, can result from this decreased adiponectin secretion (Öhlund et al., 2015; Hoenig et al., 2013).

On the other hand, reduced adiponectin levels in obesity are associated with higher inflammatory marker levels and impaired lipid metabolism, which exacerbates insulin resistance (Hoenig et al., 2013; Stenberg et al., 2023). Interestingly, research indicates that overweight cats who lose weight have more adiponectin, suggesting that weight loss efforts could help to correct certain metabolic anomalies (Takashima et al., 2016; Hoenig et al., 2013).

Like other species, insulin is necessary for energy homeostasis and glucose metabolism in cats. In cats, insulin sensitivity and glucose tolerance are significantly influenced by body weight and obesity; these two parameters are intimately linked to insulin secretion and action. The dysregulation of insulin is a critical factor in the development of metabolic disorders in obese cats, as it is a critical regulator of glucose metabolism (Strage et al., 2021). In these animals, an increase in adiposity is closely linked to a decrease in insulin sensitivity, which results in a compensatory increase in pancreatic insulin secretion. This hyperinsulinemia frequently serves as an early indicator of metabolic dysfunction, occurring prior to the development of overt hyperglycemia and clinical diabetes mellitus (Clark and Hoenig, 2021; Appleton et al., 2000b).

Research has particularly revealed that every kilo of body weight correlates to a notable drop in insulin sensitivity (Clark and Hoenig, 2021). Emphasizing that hyperinsulinemia may function as an early diagnostic indicator of the progression to diabetic conditions, obese cats have been observed to exhibit elevated plasma insulin concentrations in comparison to their ideal-weight counterparts (Appleton et al., 2000b).

Establishing precise reference ranges for hyperinsulinemia in cats remains challenging, as reported values vary considerably depending on the analytical method, physiological state, and study population (Strage et al., 2021). According to this study, baseline insulin concentrations in healthy cats ranged approximately from 2 to 18 μU/mL, depending on analytical method and physiological status (Appleton et al., 2001).

Importantly, there is no standardized threshold currently accepted for defining hyperinsulinemia in feline patients. Most authors agree that insulin values should be interpreted in light of the animal’s clinical picture, including body condition, glucose levels, and insulin-to-glucose ratios, rather than relying solely on an isolated numeric cutoff.

Gene expression research on fat cats has also exposed the molecular processes underlying insulin dysregulation. Changes in the expression of genes linked to insulin signaling and glucose metabolism in both adipose and skeletal muscle tissues have been found by Stenberg et al. (2023). These results imply that alterations at the transcriptional level brought on by obesity could help explain higher insulin secretion and compromised insulin function.

Takashima et al. molecularly cloned feline resistin and showed that it was expressed in both normal and obese cats. Resistin is known to be linked to insulin resistance in a variety of animals (Quijada et al., 2013- abstract). Although the precise routes are less known than for other species, their research showed that feline resistin levels positively linked with obesity, indicating a role in the development of insulin resistance (Takashima et al., 2016).

The involvement of another adipokine, chemerin, inflammation and metabolic control has been studied. Chemerin plays a role in immune cell recruitment and adds to the low-grade inflammation that is frequently observed in obese individuals (Recinella et al., 2020; Sierawska and Niedźwiedzka-Rystwej, 2022; Kirichenko et al., 2022). Although the precise role of chemerin in adipose tissue in cats is still unclear, new research indicates it might be a useful indicator of metabolic disorders associated with obesity (Velde et al., 2013).

Because of its insulin-sensitizing qualities, omentin may be used therapeutically to treat obesity and other metabolic diseases in cats (Appleton et al., 2000b). Omentin’s anti-inflammatory properties were emphasized by Mazaki-Tovi et al., 2019a, who also discovered a negative correlation between its concentrations and body fat percentage, indicating a preventive function against the metabolic problems associated with obesity.

Although it belongs to a family of adipokines important in metabolic control, CTRP-12 is less well-studied in cats than in humans and rodents. Although further research is required to validate these results, some research indicates that CTRP-12 may improve lipid metabolism and insulin sensitivity, which could help manage obesity in cats (Luo et al., 2023).

The intricate and multiple routes by which excess body fat causes insulin resistance and the onset of type 2 diabetes in cats represent the interactions among adipose tissue, adipokines, inflammation, and glucose metabolism. Many metabolic changes caused by increasing body fat, particularly visceral fat, promote insulin resistance, a condition defined by a reduced capacity of insulin-responsive tissues to react to the effects of insulin (Cook and Evans, 2021). Obesity is related to changes in the release of adipokines, which are signaling proteins produced by adipose tissue. While insulin-sensitizing adipokines like adiponectin are lower, pro-inflammatory adipokines such as leptin and TNF-alpha are markedly raised in obese cats (Hoenig et al., 2013; Araújo et al., 2024). A persistent low-grade inflammatory state brought on by excessive inflammatory cytokine levels that harm insulin signaling pathways and disrupt insulin’s normal metabolic functions causes increased insulin resistance and compromised glucose uptake in peripheral tissues (Zini et al., 2008). Hyperglycemia is exacerbated as a result of the liver and muscle tissues losing their sensitivity to insulin and in order to maintain normal glucose levels in the face of chronic insulin resistance, the pancreatic beta cells must produce more insulin. Insulin secretion capacities may be further compromised over time by beta-cell fatigue and malfunction brought on by the increased demand for insulin synthesis (Abdullah et al., 2010; Osto et al., 2013; Zini et al., 2008). Long-term exposure to insulin-resistant hyperglycemia in cats can cause glucotoxicity, which damages beta cells and reduces their capacity to produce insulin efficiently, the mechanism is illustrated in Figure 2 (Zini et al., 2008; Osto et al., 2013). Because of decreased glucose clearance associated with insulin resistance, postprandial glucose levels in obese cats stay noticeably higher for longer periods of time (Hoenig et al., 2011a; Appleton et al., 2000b).

These metabolic abnormalities point to a general decrease in glucose tolerance, which accelerates the development of type 2 diabetes. Inflammation connected to obesity disrupts insulin signaling and raises oxidative stress in tissues. High reactive oxygen species (ROS) damaging insulin signaling pathways can help to build a feedback loop maintaining metabolic inefficiency and insulin resistance (Clark and Hoenig, 2021; Zagayko et al., 2019).

The development and worsening of obesity in cats are largely caused by lifestyle factors, particularly a sedentary lifestyle and the consumption of high-calorie, nutrient-poor diets (Kocabağlı et al., 2017; Öhlund et al., 2015).

Dogs and cats have quite different adipose tissues in terms of composition, function, and the type of adipokines they release, which affect inflammation and metabolism. Adipocytes in dogs and cats react differently to nutritional elements and inflammatory stimuli, which can result in significant differences in the properties of their adipose tissue (Osto and Lutz, 2015).

According to research, inflammatory triggers such as lipopolysaccharides (LPS) and tumor necrosis factor-alpha (TNFα) cause adipocytes in dogs to release pro-inflammatory adipokines. For example, Ryan et al. pointed out that canine adipose cells produce inflammatory adipokines such leptin and interleukin-6 (IL-6), which may play a significant part in inflammation linked to obesity (Ryan et al., 2010). Additionally, Mazaki-Tovi et al. (2018) found that dietary fatty acids may alter the release of IL-6 and adiponectin in canine adipose tissue, suggesting that food has a direct impact on inflammatory responses and adipokine profiles. Essentially, dogs have a reactive adipose tissue phenotype, which may be a factor in disorders linked to obesity.

In contrast, the situation regarding inflammation and adipokine expression in feline adipose tissue is different. Although research shows that high-fat diets mostly increase oxidative stress rather than inflammation in their adipose depots, cats still tend to develop obesity-associated adipose tissue inflammation (Ampem et al., 2015; Osto and Lutz, 2015). Their metabolic responses may be impacted by this divergence; notable variations have been observed in the cytokine composition of adipose tissue, especially in the expression pathways that control insulin sensitivity. According to Stenberg et al., the metabolic changes in feline adipose tissue might be the result of a special evolutionary trajectory in which cats, as obligate carnivores, have different energy-storage systems than dogs (Stenberg et al., 2023).

Of their investigation of the gene expression profiles of feline adipocytes, Riedel et al. discovered unique renin-angiotensin system regulation patterns that are less noticeable in canine adipose tissues (Riedel et al., 2015). Adipokines may play different roles in regulating inflammation and energy metabolism in diverse species, as suggested by these variations. According to James et al. (2017), some adaptive responses of cats to energy mobilization and storage during times of excess or fasting have consequences for understanding how susceptible they are to metabolic diseases in comparison to dogs.

Additionally, the two species differ in the functional capacities of mesenchymal stem cells generated from adipose tissue. According to characterization studies, mesenchymal stem cells from adipose tissue in both species can differentiate into distinct lineages, but their properties and efficiency may vary depending on the tissue source. To further clarify the unique biological traits originating from their adipose tissues, Rashid et al. (2021) for instance, described the differences between the mesenchymal stem cells of dogs and cats with regard to their capacity for proliferation and differentiation (Rashid et al., 2021).

Research suggests that a high-protein diet can lower pro-inflammatory adipokines like TNF-alpha and IL-6 while raising healthy adipokines like adiponectin. High-protein diets have been shown to raise serum levels of adiponectin, which have insulin-sensitizing properties, in cats (Berman et al., 2021; Öhlund et al., 2021). Adiponectin is essential for increasing insulin sensitivity because it increases muscle glucose absorption and encourages fatty acid oxidation. Diets heavy in protein have also been connected to better glycemic control since higher protein consumption raises postprandial blood glucose levels (Grant et al., 2020; Clark and Hoenig, 2021).

Although high-protein diets are often linked to concerns about renal stress, certain studies indicate they may offer advantages in particular contexts, for instance, in helping cats preserve muscle mass during the early stages of chronic kidney disease (Hall et al., 2019). These findings emphasize that the impact of dietary protein on kidney function is not uniform and must be evaluated in relation to each cat’s medical profile. Notably, Kubo et al. (2023) found no harmful renal effects in healthy subjects consuming high-protein diets, suggesting that cats without kidney compromise may better tolerate elevated protein intake (Grant et al., 2020).

Given protein’s fundamental role in feline health, adjusting intake based on individual health status is essential, especially in aging cats or those with existing renal issues. The interplay between protein metabolism, phosphorus levels, and kidney response reinforces the need for tailored nutritional plans that take into account each cat’s unique vulnerabilities.

Studies show that cats’ glucose metabolism may be negatively impacted by high-carb diets. According to a study, cats who consume high-carb diets nonetheless have a less ideal metabolic state even though they do not cause β-cell malfunction like some other animals do. According to Hewson-Hughes et al. (2011), a high carbohydrate content was particularly linked to increased postprandial glucose and insulin levels, which started debates on the relevance of dietary composition in controlling cat diabetes (Verbrugghe and Hesta, 2017; Hoenig et al., 2011a; Laflamme et al., 2022).

Compared to conventional high-carb diets, low-carb diets can frequently result in more noticeable improvements in insulin sensitivity. In order to diminish insulin resistance, these diets are associated with lower serum insulin levels and less body fat accumulation. According to research, meals high in protein and low in carbohydrates may increase insulin signaling pathways, which in turn may improve glucose metabolism, better lipid profiles and a lower incidence of fatty liver disease, which is frequently a result of metabolic disturbances linked to obesity (Asaro et al., 2017; Mazaki-Tovi et al., 2013; Tricò et al., 2021; Doostvandi, 2016). These dietary changes can help in reestablishing the proper balance of adipokines by lowering pro-inflammatory cytokines and raising levels of anti-inflammatory adipokines.

High-protein, low-carbohydrate diets have been associated with improvements in insulin sensitivity and metabolic regulation in obese cats (Coradini et al., 2011). These dietary approaches influence adipokine profiles, often resulting in reduced leptin levels and increased adiponectin concentrations, thereby contributing to a lower leptin–adiponectin ratio (LAR), a marker increasingly recognized for its association with insulin resistance (Appleton et al., 2000b; Mazaki-Tovi et al., 2019a). Since a high LAR has been linked to metabolic dysfunction and inflammation, nutritional strategies that restore adipokine balance may enhance metabolic outcomes. This effect supports the potential use of LAR not only as a biomarker of metabolic status, but also as a target for monitoring response to dietary interventions (Stenberg et al., 2023).