Is leptin resistance the cause or the consequence of diet-induced obesity?

de, Kathy C G; Peterse, Céline; Beerens, Sanne; Luijendijk, Mieneke C. M.; Plasse, G; Fleur, Susanne E. la; Adan, Roger A.H.

doi:10.1038/s41366-018-0111-4

Cited by 30 publications

(40 citation statements)

References 46 publications

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“…Interestingly, baseline leptin sensitivity on a CD, although not total caloric intake or differences in diet component preference, predicted subsequent weight gain when switched to a fc-HFHS diet. 40 In contrast to the rapid onset of leptin unresponsiveness observed in one study after 7 days of fc-HFHS diet, 34 we now observed leptin resistance after 28 but not 14 days of fc-HFHS diet consumption. 40 These differences might be explained by different methodology.…”

Section: Leptin Dynamics and Neuroinflammationcontrasting

confidence: 65%

“…Consumption of a fc-HFHS, for up to 6 months, increases total body weight gain compared to CD controls, and this was associated with profound increases in abdominal and subcutaneous white adipose tissue (WAT) mass. [33][34][35][36][37][38][39][40][41][42] Male Wistar or Sprague-Dawley rats with access to a fc-HF or fc-HS diet consistently show no or very limited effects on total body weight gain compared to CD controls, despite increases in terminal WAT mass. [33][34][35][36][37] When female Sprague-Dawley rats were maintained on a fc-HFHS diet containing a solution with maltodextrin, a polysaccharide composed of chains of glucose, for up to 36 weeks, increases in body weight gain and persistent hyperphagia were also observed.…”

Section: Effects Of Fc-hfhs Diets On Body Weight and White Adipose mentioning

confidence: 99%

“…Consumption of a fc-HFHS diet, for up to 8 weeks, results in persistent hyperphagia compared to CD controls in male Wistar rats and C57BL/6J mice. [33][34][35][36][37][38][39][40][41]47 Similarly, providing female Sprague-Dawley rats with a fc-HFHS diet, containing a maltodextrin solution, for up to 36 weeks also results in persistent hyperphagia. 43 By contrast, exposure to nc-HFDs or nc-HFHS diets results in transient caloric overconsumption, with caloric intake usually returning to CD control levels between 1 and 3 weeks after initial exposure to the diet.…”

Section: Effects Of Fc-hfhs Diets On Total Caloric Consumptionmentioning

confidence: 99%

“…[34][35][36][37] Collectively, these consistent observations indicate that simultaneous access to individual fat (eg, beef tallow) and sugar solution diet components of the fc-HFHS diet is required to induce persistent hyperphagia compared to CD controls. Notably, both rats [33][34][35][36][37][38][39][40][41] and mice 47 demonstrate persistent caloric overconsumption. Because rats and mice are were given access to slightly different versions of the fc-HFHS diet, these observations indicate that fc-HFHS diet-induced persistent hyperphagia is independent of the sugar source of the solution (sucrose vs maltodextrin solutions), the caloric content of the sucrose solution (30% vs 10% dilution) or the caloric fat content of the CD (18% vs 12% kcal from fat).…”

Section: Effects Of Fc-hfhs Diets On Total Caloric Consumptionmentioning

confidence: 99%

“…Despite this temporal and relative high intake of fat, the intake of all individual diet components is generally quite stable over time for each animal. 33,35,36,40 However, rats do show substantial inter-individual variability in their preference for the different fc-HFHS diet components. As a result, it is important that experiments with free-choice diets should be based on a robust experimental design that accounts for this baseline variability to attain statistical power.…”

Section: Effects Of Fc-hfhs Diets On Diet Component Selectionmentioning

confidence: 99%

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Stressing the importance of choice: Validity of a preclinical free‐choice high‐caloric diet paradigm to model behavioural, physiological and molecular adaptations during human diet‐induced obesity and metabolic dysfunction

Slomp

Belegri

Blancas-Velazquez

et al. 2019

J Neuroendocrinology

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Humans have engineered a dietary environment that has driven the global prevalence of obesity and several other chronic metabolic diseases to pandemic levels. To prevent or treat obesity and associated comorbidities, it is crucial that we understand how our dietary environment, especially in combination with a sedentary lifestyle and/or daily‐life stress, can dysregulate energy balance and promote the development of an obese state. Substantial mechanistic insight into the maladaptive adaptations underlying caloric overconsumption and excessive weight gain has been gained by analysing brains from rodents that were eating prefabricated nutritionally‐complete pellets of high‐fat diet (HFD). Although long‐term consumption of HFDs induces chronic metabolic diseases, including obesity, they do not model several important characteristics of the modern‐day human diet. For example, prefabricated HFDs ignore the (effects of) caloric consumption from a fluid source, do not appear to model the complex interplay in humans between stress and preference for palatable foods, and, importantly, lack any aspect of choice. Therefore, our laboratory uses an obesogenic free‐choice high‐fat high‐sucrose (fc‐HFHS) diet paradigm that provides rodents with the opportunity to choose from several diet components, varying in palatability, fluidity, texture, form and nutritive content. Here, we review recent advances in our understanding how the fc‐HFHS diet disrupts peripheral metabolic processes and produces adaptations in brain circuitries that govern homeostatic and hedonic components of energy balance. Current insight suggests that the fc‐HFHS diet has good construct and face validity to model human diet‐induced chronic metabolic diseases, including obesity, because it combines the effects of food palatability and energy density with the stimulating effects of variety and choice. We also highlight how behavioural, physiological and molecular adaptations might differ from those induced by prefabricated HFDs that lack an element of choice. Finally, the advantages and disadvantages of using the fc‐HFHS diet for preclinical studies are discussed.

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Section: Leptin Dynamics and Neuroinflammationcontrasting

confidence: 65%

Section: Effects Of Fc-hfhs Diets On Body Weight and White Adipose mentioning

confidence: 99%

Section: Effects Of Fc-hfhs Diets On Total Caloric Consumptionmentioning

confidence: 99%

Section: Effects Of Fc-hfhs Diets On Total Caloric Consumptionmentioning

confidence: 99%

Section: Effects Of Fc-hfhs Diets On Diet Component Selectionmentioning

confidence: 99%

See 3 more Smart Citations

Stressing the importance of choice: Validity of a preclinical free‐choice high‐caloric diet paradigm to model behavioural, physiological and molecular adaptations during human diet‐induced obesity and metabolic dysfunction

Slomp

Belegri

Blancas-Velazquez

et al. 2019

J Neuroendocrinology

Self Cite

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Individual Differences in Behavioral Responses to Palatable Food or to Cholecystokinin Predict Subsequent Diet‐Induced Obesity

Wald

Grill

2019

Obesity

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Objective This study investigated whether individual differences in behavioral responses to palatable food and to the satiation signal cholecystokinin (CCK) in outbred chow‐maintained Sprague‐Dawley rats enabled prediction of individual differences in weight gained after subsequent high‐fat/high‐sugar diet (HFHSD) maintenance. Methods Meal size, meal number, and early dark cycle intake during initial HFHSD exposure were measured, as were early dark cycle sucrose solution and chow intake, chow meal size and meal number, the intake‐suppressive effects of 0.5‐µg/kg CCK injection, and CCK‐induced c‐Fos activation in the nucleus tractus solitarius. Subsequently, rats were maintained on an HFHSD for 5 weeks, and weight gain was determined. Results Rats that took larger and less frequent meals on the first day of HFHSD exposure, whose early dark cycle intake (HFHSD and sucrose) was larger during initial HFHSD exposure, gained more weight after HFHSD maintenance. Rats with lesser sucrose intake suppression in response to CCK gained more weight after HFHSD maintenance and displayed reduced CCK‐induced c‐Fos activation in the nucleus tractus solitarius. Conclusions Together, these data identify individual differences in behavioral responses to palatable food and to CCK as novel predictors of diet‐induced obesity.

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Safflower yellow and its main component hydroxysafflor yellow A alleviate hyperleptinemia in diet‐induced obesity mice through a dual inhibition of the GIP‐GIPR signaling axis

Lyu

Yan

et al. 2023

Phytotherapy Research

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Glucose‐dependent insulinotropic polypeptide (GIP) is a gastrointestinal hormone secreted by K cells in the small intestine and is considered an obesity‐promoting factor. In this study, we systematically investigated the anti‐obesity effects of intragastric safflower yellow (SY)/hydroxysafflor yellow A (HSYA) and the underlying mechanism for the first time. Our results showed that intragastric SY/HSYA, rather than an intraperitoneal injection, notably decreased serum GIP levels and GIP staining in the small intestine in diet‐induced obese (DIO) mice. Moreover, intragastric SY/HSYA was also first found to significantly suppress GIP receptor (GIPR) signaling in both the hypothalamus and subcutaneous White adipose tissue. Our study is the first to show that intragastric SY/HSYA obviously reduced food intake and body weight gain in leptin sensitivity experiments and decreased serum leptin levels in DIO mice. Further experiments demonstrated that SY treatment also significantly reduced leptin levels, whereas the inhibitory effect of SY on leptin levels was reversed by activating GIPR in 3 T3‐L1 adipocytes. In addition, intragastric SY/HSYA had already significantly reduced serum GIP levels and GIPR expression before the serum leptin levels were notably changed in high‐fat‐diet‐fed mice. These findings suggested that intragastric SY/HSYA may alleviate diet‐induced obesity in mice by ameliorating hyperleptinemia via dual inhibition of the GIP‐GIPR axis.

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Is leptin resistance the cause or the consequence of diet-induced obesity?

Abstract: A pre-existing reduction in leptin sensitivity determines the susceptibility to develop excessive DIO after fcHFHS diet exposure. Rats with a pre-existing reduction in leptin sensitivity develop excessive DIO without eating more calories or altering their leptin sensitivity.

Cited by 30 publications

References 46 publications

Stressing the importance of choice: Validity of a preclinical free‐choice high‐caloric diet paradigm to model behavioural, physiological and molecular adaptations during human diet‐induced obesity and metabolic dysfunction

Stressing the importance of choice: Validity of a preclinical free‐choice high‐caloric diet paradigm to model behavioural, physiological and molecular adaptations during human diet‐induced obesity and metabolic dysfunction

Individual Differences in Behavioral Responses to Palatable Food or to Cholecystokinin Predict Subsequent Diet‐Induced Obesity

Safflower yellow and its main component hydroxysafflor yellow A alleviate hyperleptinemia in diet‐induced obesity mice through a dual inhibition of the GIP‐GIPR signaling axis

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