Studies examining the effects of low-protein diets on food intake and body weight have shown varied results. Many researchers have found low dietary protein to increase food intake, while others have found no effect or even a decrease. In 63 male Sprague-Dawley rats, we examined several low levels of dietary protein (2%, 5%, 8%, 10%, 15% vs. 20% casein) to determine the dose-response relationships between low dietary protein and food intake, body composition, energy balance and serum leptin concentrations. Food intake, over the range of low dietary protein, showed a quasi bell-shaped response curve with peak intake occurring in rats fed 8-10% casein. Peak feeding occurred at or just below the estimated protein requirement of the rats (10-12.5% casein). Compared to the 20% casein controls, food intake was severely reduced in rats fed 2% casein, while it was greater in the other low-protein groups. The amount of body fat steadily increased between the 15% casein group and the 8% casein group, and sharply declined between the 5% casein group and 2% casein group. The change in body fat reflected both the change in food intake and altered energy partitioning. Serum leptin concentrations were greater in rats fed the 5 and 8% casein diets than in control rats fed 20% casein. Serum leptin concentrations were positively associated with body fat content (r(2) = 0.763, P < 0.001). Increased serum leptin concentrations in the presence of increased food intake is suggestive of a state of leptin resistance. This animal model may provide important insights into diet-induced obesity.

White. Central leptin increases insulin sensitivity in streptozotocin-induced diabetic rats. Am J Physiol Endocrinol Metab 282: E1084-E1091, 2002; 10.1152/ajpendo.00489.2001.-This study examined the effect of intracerebroventricular leptin on insulin sensitivity in streptozotocin (STZ)-induced diabetic rats. Male Wistar rats were cannulated in the lateral ventricle and, after recovery, administered either intravenous STZ (50 mg/kg) to induce diabetes or citrate buffer. Chronic leptin (10 g/10 l icv) or vehicle injections were administered daily for 14 days beginning 2 days after establishment of hyperglycemia in the diabetic animals. At the end of the 2 wk of injections, insulin sensitivity was measured by the steady-state plasma glucose (SSPG) method. Blood glucose concentrations were dramatically reduced and normalized by the 4th day in diabetic animals receiving intracerebroventricular leptin treatment. Diabetic animals exhibited insulin resistance, whereas intracerebroventricular leptin significantly enhanced insulin sensitivity, as indicated by decreased SSPG. Circulating leptin levels were not increased in animals injected with intracerebroventricular leptin. Thus the increased peripheral insulin sensitivity appears to be due solely to the presence of leptin in the brain, not to leptin acting peripherally. These data imply that inadequate central leptin signaling may lead to insulin resistance. intracerebroventricular leptin; insulin resistance; hyperglycemia THE INTERACTION BETWEEN LEPTIN AND INSULIN has been the subject of several investigations. Leptin is thought to be a signal that informs the brain about the size of the fat mass in the body. It acts as a satiety factor, decreasing food intake and increasing energy expenditure, or at least preventing the decrease in energy expenditure normally associated with a decrease in food intake (38). These effects lead to a decrease in body fat. In addition to these actions, leptin treatment enhances insulin sensitivity in normal rats, as indicated by increased insulin-stimulated glucose utilization in peripheral tissues (7,33,42). It also decreases plasma glucose and/or insulin concentrations of normal animals in the postabsorptive state. Leptin has been shown to directly inhibit insulin secretion (11), whereas insulin increases leptin release from adipocytes (25). Evidence indicates that glucose metabolism, rather than insulin itself, is the main determinant for leptin expression in adipose tissue (22). Moreover, in vivo and in vitro evidence suggests that leptin and insulin-signaling networks may be connected at several levels, such as insulin receptor substrates, or IRS; phosphatidylinositol 3-kinase, or PI 3-kinase; and mitogen-activated protein kinase, or MAPK (19,20,41). Therefore, leptin and insulin-signaling pathways may interact with each other.The effects of leptin on insulin sensitivity have been examined independently of peripheral insulin concentrations. Diabetic animals induced by streptozotocin (STZ), which selectively destroys insulin-producing...

Previous investigations have demonstrated a marked effect of soy protein on the metabolic syndrome (MS). The purpose of this preliminary study was to identify the effects of soy-based diets on male obese ZDFxSHHF (fa/ fa-cp/?) rats. Animals were randomly assigned to one of four diets: control, casein (C); low-isoflavone (LIS) soy protein; high-isoflavone (HIS) soy protein; or casein + rosiglitazone (CR). Physiological, biochemical, and molecular parameters were determined at sacrifice. Body weight (p < 0.01) and food intake (p < 0.05) were lower in LIS-fed rodents. Rosiglitazone-treated animals had higher body weight and adiposity (p < 0.05). LIS and CR groups exhibited better glycemic control (p < 0.05), but with a limited effect in rosiglitazone-treated animals. HIS fed rats had higher glucose and triacylglyceride levels (p < 0.01), and lower plasma insulin (p < 0.01). Renal function parameters with the exception of an increase in systolic blood pressure (p < 0.05) were all suppressed in the LIS group (p < 0.01). The CR group had twofold PPARalpha and PPARgamma mRNA abundance (p < 0.01). LIS-fed animals also exhibited greater abundance of PPARgamma mRNA (p < 0.001), and nearly threefold FAS and CPT-1 mRNA levels (p < 0.05). HIS-fed rats also had higher abundance of CPT-1 mRNA, as well as a lower abundance of ACC mRNA (p < 0.05). Soy-based diets, influenced by isoflavone content and distinct from rosiglitazone, improved several metabolic parameters in obese ZDFxSHHF rats.

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Previous investigations have demonstrated a marked effect of soy protein on multiple physiological parameters associated with the metabolic syndrome (MS). This preliminary study investigated the physiological effects of soy-based diets on cardiovascular risk in a unique rodent model that reflects early stages of MS. Briefly, lean male SHHF (+/cp) rats were randomly assigned to the following treatment groups: casein (control, C); low-isoflavone (LIS) soy protein isolate; high-isoflavone (HIS) soy protein isolate; or C+ 0.01 % rosiglitazone (CR). Rats were fed for thirty-six weeks. Liver weight, heart weight, total plasma cholesterol, fasting blood glucose were lower in soy-fed animals compared to control (p < 0.01). Body weight, kidney weight, alanine aminotransferase (ALT), fasting plasma insulin, and homeostasis model assessment (HOMA) score were also lower in LIS-fed rodents (p < 0.05) compared to casein treatment. All diet groups exhibited lower urine protein (p < 0.01) and small arteriole content (p < 0.05) compared to controls. LIS feed had a slightly more profound influence on body weight, liver metabolism, and insulin sensitivity. However, both soy diets exhibited marked improvements over a casein-based diet.