Effects of consuming a high carbohydrate diet after eight weeks of exposure to a ketogenic diet

<p>Abstract</p> <p>Background</p> <p>Ketogenic diets have been utilized for weight loss and improvement in metabolic parameters. The present experiments examined the effects of returning to a chow diet after prolonged ingestion of a ketogenic diet.</p> <p>Methods</p> <p>Rats were maintained on chow (CH) or a ketogenic diet (KD) for 8 weeks, after which the KD rats were given access to chow only (KD:CH) for 8 additional weeks. Caloric intake, body weight, and plasma leptin, insulin and ghrelin were measured before and after the dietary switch.</p> <p>Results</p> <p>After 8 weeks of consuming a ketogenic diet, KD rats had increased adiposity and plasma leptin levels, and reduced insulin, as compared to CH controls. One week after the diet switch, fat pad weight and leptin levels remained elevated, and were normalized to CH controls within 8 weeks of the dietary switch. Switching from KD to chow induced a transient hypophagia, such that KD:CH rats consumed significantly fewer calories during the first week after the dietary switch, as compared to calories consumed by CH rats. This hypophagia was despite significantly increased plasma ghrelin in KD:CH rats. Finally, KD:CH rats developed hyperphagia over time, and during weeks 6-8 after the diet switch consumed significantly more calories per day than did CH-fed controls and gained more weight than CH-fed controls.</p> <p>Conclusion</p> <p>Collectively, these data demonstrate that returning to a carbohydrate-based diet after a period of consuming a ketogenic diet has post-diet effects on caloric intake, body weight gain, and insulin levels.</p

Endocrine effects of a low-carbohydrate, high-fat ketogenic diet

Low-carbohydrate, high-fat ketogenic diets (KD) have become popular in recent years and are often used in an effort to control body weight. Our laboratory examines how maintenance on a ketogenic diet affects the multiple peripheral and central neuroendocrine systems involved in the regulation of energy balance in rats. We have previously observed increases in epididymal fat pad weight, and plasma leptin and ghrelin concentrations, as well as decreases in plasma insulin concentrations following a 7-week KD. The present series of experiments explored the development of changes in plasma endocrine hormone profiles over the course of an 8-week KD and the endocrine effects of returning to a chow diet (CH) following 8 weeks of KD consumption. Rats were maintained on CH or KD and sacrificed after 1, 4, or 8 weeks of diet maintenance (Experiment 1). We found significant increases in epididymal fat pad weight only after the full duration of KD maintenance. Plasma leptin levels were also elevated in KD rats. Contrary to previous studies, the present experiment did not observe alterations in plasma insulin or ghrelin levels. In Experiment 2, rats were maintained on CH or KD for a total of 8 weeks. Following this time, KD rats were switched to consuming CH and sacrificed after 1, 4, or 8 weeks of CH feeding (9, 12, and 16 total weeks). Results were compared to data collected after 8 weeks of maintenance on the original assigned diet. We observed increases in caloric intake and plasma insulin concentrations following the switch from KD to CH, starting at weeks 14 and 16, respectively. Epididymal fat pad weights and plasma leptin concentrations remained at levels exhibited at the end of KD maintenance following the diet switch. The present series of experiments demonstrates the ability of KD to produce alterations in plasma endocrine hormones not only during diet maintenance, but also following the switch to an alternative diet

Role of insulin dysregulation in the development of yoshida sarcoma-induced cancer cachexia

Cancer cachexia is a devastating syndrome present in many individuals with cancer. Characterized by weight loss, loss of appetite, and wasting of skeletal muscle and adipose tissue, cachexia is associated with an increase in both morbidity and mortality in this population. The majority of individuals with cancer will experience some degree of cachexia during the course of their disease, making cachexia a clinically relevant syndrome for which the contributing mechanisms are largely unknown. A decline in insulin function, as measured by reduced glucose tolerance and insulin sensitivity, is common in individuals with and animal models of cancer cachexia. The present series of experiments was designed to examine the role of this insulin dysregulation in the development of cancer cachexia in rats bearing the Yoshida sarcoma. In experiment 1, insulin sensitivity was measured during the tumor growth period to determine when insulin dysregulation begins, relative to changes in body composition associated with cancer cachexia (Chapter 2). In Experiment 2, control and tumor-bearing animals were treated daily with saline or Exnedin-4, a GLP-1 agonist, in order to determine whether cachexia could be prevented by improving insulin sensitivity (Chapter 3). In Experiment 3, animals were fed a chow diet or a high-fat diet prior to tumor implantation, to determine if diet-induced insulin resistance modifies the development of cachexia in rats bearing the Yoshida sarcoma (Chapter 4). Our results indicate that 1) insulin dysregulation is present in Yoshida sarcoma-bearing rats prior to the onset of cachexia, 2) prevention of insulin dysregulation via chronic Exendin-4 treatment prevents the development of some cancer cachexia symptoms, and 3) the induction of insulin dysregulation via high-fat diet feeding accelerates the development of cancer cachexia. Further research is necessary to determine the mechanisms through which insulin dysregulation develops, as alterations in insulin signaling do not appear to contribute significantly to the observed effects

Sensitivity to the Anorectic Effects of Leptin Is Retained in Rats Maintained on a Ketogenic Diet despite Increased Adiposity

BACKGROUND: Rats maintained on a ketogenic diet (KD; 80% fat, 15% protein, 5% carbohydrate) have increased adiposity and leptin as compared to chow-fed controls (CH; 16% fat, 19% protein, 65% carbohydrate), although body weights and daily caloric intakes do not differ. METHODS: Rats maintained on a KD or CH were assessed for responsivity to intraperitoneal (i.p.) or intracerebroventricular (i.c.v.) leptin. Hypothalamic gene expression was evaluated to determine the effects of KD on proopiomelanocortin (POMC) mRNA expression and components of the leptin-signaling system. RESULTS: Caloric intake by KD rats was decreased at a lower dose of i.p. leptin (100 μg) than was required to reduce intake by CH rats (leptin, caloric intake was reduced in KD rats as compared to intake following i.p. saline; p < 0.05). In a separate experiment to evaluate responsivity to i.c.v. leptin, the minimal dose of leptin required to significantly reduce 24-hour caloric intake did not differ between the groups. In the arcuate nucleus, POMC mRNA was elevated after a lower dose of i.c.v. leptin in KD rats (5 μg) than was required to increase POMC mRNA expression in CH rats (15 μg) or reduce caloric intake in either group. Finally, evaluation of the level of phosphorylated STAT3 (pSTAT3) in the arcuate and SOCS3 mRNA in the hypothalamus revealed significantly more pSTAT3-positive cells and increased SOCS3 mRNA expression at baseline for KD rats, compared to CH, neither of which was further increased following i.p. leptin administration. CONCLUSION: These data demonstrate that despite increased adiposity, leptin and markers of leptin resistance, responsivity to the anorectic effects of exogenous leptin is retainable during maintenance on a KD

Insulin Sensitivity and Glucose Tolerance Are Altered by Maintenance on a Ketogenic Diet

Low-carbohydrate, ketogenic diets (KD) are frequently implemented in efforts to reduce or maintain body weight, although the metabolic effects of long-term exposure to this type of diet remain controversial. This study assessed the responsivity to peripheral and central insulin, glucose tolerance, and meal-induced effects of consuming a KD in the rat. After 8 wk of consuming chow or KD, caloric intake after peripheral or central insulin and insulin and glucose levels after a glucose challenge were assessed. In a separate group of rats, glucose and insulin responses to either a low- or high-carbohydrate test meal were measured. Finally, rats maintained on KD were switched back to a chow diet, and insulin sensitivity and glucose tolerance were evaluated to determine whether the effects of KD were reversible. Maintenance on KD resulted in decreased sensitivity to peripheral insulin and impaired glucose tolerance. Furthermore, consumption of a high-carbohydrate meal in rats that habitually consumed KD induced significantly greater insulin and glucose levels for an extended period of time, as compared with chow-fed controls. Responsivity to central insulin was heightened in KD rats and associated with increased expression levels of insulin receptor mRNA. Finally, returning to a chow diet rapidly reversed the effects of KD on insulin sensitivity and glucose tolerance. These data suggest that maintenance on KD negatively affects glucose homeostasis, an effect that is rapidly reversed upon cessation of the diet