Effect of Combined Excess Iodine and Low-Protein Diet on Thyroid Hormones and Ultrastructure in Wistar Rats

The aim of the present study was to illustrate the combined effect of excess iodine and low-protein diet on the thyroid, and the potential molecular mechanism of this effect. One hundred ninety-two Wistar rats were randomly divided into the following groups: normal; 10- (10HI), 50- (50HI), or 100-fold excess iodine (100HI); low-protein; and low-protein combined with 10- (L10HI), 50- (L50HI), or 100-fold excess iodine (L100HI). At the end of 2, 4, or 6 months, the rats were sacrificed for iodine concentration and thyroid hormone analyses. The histological appearance of the thyroid gland was observed at the end of 6 months. At the end of 6 months, the serum total thyroxine (TT₄), free thyroxine (FT₄), total triiodothyronine (TT₃), and free triiodothyronine (FT₃) levels in the 100HI, L10HI, L50HI, and L100HI groups were significantly lower than the control group (P?<?0.05 or P?<?0.01). Serum TT₄, FT₄, TT₃, and FT₃ levels in the low-protein excess iodine groups were significantly lower than the groups with an equal amount of excess iodine alone (P?<?0.05 or P?<?0.01). Light and electron microscopy showed that excess iodine caused damage to the ultrastructure of thyroid and apoptosis of follicular epithelial cells. In the 100HI, L50HI, and L100HI groups, thyroid follicular epithelial cells became flattened, and follicles became distended with colloid. The damage was more serious in low-protein groups. The present findings demonstrated that the low-protein diet aggravated the damage to the thyroid caused by excess iodine alone.     

Smaller Fixation Target Size Is Associated with More Stable Fixation and Less Variance in Threshold Sensitivity

The aims of this randomized observational case control study were to quantify fixation behavior during standard automated perimetry (SAP) with different fixation targets and to evaluate the relationship between fixation behavior and threshold variability at each test point in healthy young participants experienced with perimetry. SAP was performed on the right eyes of 29 participants using the Octopus 900 perimeter, program 32, dynamic strategy. The fixation targets of Point, Cross, and Ring were used for SAP. Fixation behavior was recorded using a wearable eye-tracking glass. All participants underwent SAP twice with each fixation target in a random fashion. Fixation behavior was quantified by calculating the bivariate contour ellipse area (BCEA) and the frequency of deviation from the fixation target. The BCEAs (deg²) of Point, Cross, and Ring targets were 1.11, 1.46, and 2.02, respectively. In all cases, BCEA increased significantly with increasing fixation target size (p < 0.05). The logarithmic value of BCEA demonstrated the same tendency (p < 0.05). A positive correlation was identified between fixation behavior and threshold variability for the Point and Cross targets (ρ = 0.413–0.534, p < 0.05). Fixation behavior increased with increasing fixation target size. Moreover, a larger fixation behavior tended to be associated with a higher threshold variability. A small fixation target is recommended during the visual field test.     

Effect of Amino Acid Supplementation to a Rice Diet on Niacin Requirement of Rats

The effect of amino acid supplementation to a rice diet on the niacin requirement of rats was studied in relation to the phenomenon of niacin or tryptophan deficiency caused by the addition of threonine or gelatin to a low casein diet. Supplementation of a mixture of all limiting amino acids other than tryptophan to a 90% rice diet stimulated the growth of rats only temporarily without additional supplementation of niacin. However, the supplementation of the same mixture of limiting amino acids to a diet containing an amino acid mixture simulating rice protein, clearly decreased the growth of rats after a temporary increase. The growth was then remarkably improved by the further addition of niacin or niacin plus tryptophan. This result supports the hypothesis that the addition of all limiting amino acids other than tryptophan, increases the use of tryptophan for protein synthesis and may lead to niacin deficiency.     

Introduction of Daytime Feeding in Rats by Exposure to Choice of a Sugar Diet

Food intakes of rats having first access to either sucrose or fructose as the carbohydrate source in a three-way selection of macronutrients were compared. In the first period of choice between sugar, protein and fat similar day/night intakes were found in rats given sucrose or fructose. When rats had a first experience with either sucrose or fructose as the carbohydrate source, their total energy and macronutrient intakes decreased dramatically and diurnal rather than nocturnal feeding occurred when sugar was switched. These findings indicate that a previous adaptation to a sugar as a carbohydrate source in a three-way selection design has long-lasting effects on the subsequent pattern and amount of food intake on a similar choice among diets.     

Factors that Affect Pancreatic Islet Cell Autophagy in Adult Rats: Evaluation of a Calorie-Restricted Diet and a High-Fat Diet

Aging may be a risk factor for type 2 diabetes in the elderly. Dietary intervention can affect glucose tolerance in adults, which may be due to body composition and islet cell autophagy. The aim of this study was to determine the effects of various dietary interventions on islet cell autophagy. Pancreatic tissue and blood samples were collected from Sprague Dawley rats (14–16 months old, n = 15 for each group) that received a normal diet (ND), a high-fat diet (HFD), or a calorie-restricted diet (CRD). The body weight (BW), visceral fat, serum lipid levels, fasting serum glucose, insulin levels, and β/α cell area were determined in 14-16-(0-w), 16-18-(8-w), and 18-20(16-w)-month-old rats. Pancreatic islet autophagy (LC3B and LAMP2), AP (Acid Phosphatase) and apoptosis (apoptosis index, AI (TUNEL assay) and cleaved caspase-3) were detected using immunohistochemistry, ELISA and western blot. At 16 weeks, the expressions of LC3B, LAMP2 and AP markedly increased in both the HFD (P<0.01) and CRD (P<0.05) groups; however, an increase in the AI (P<0.05), cleaved caspase-3 and Beclin1 expression and a decrease in the expressions of BCL2 and BCLXL (P<0.05) were observed in only the HFD group. FFA, triglyceride levels, HOMA-IR, insulin levels and glucagon levels were significantly increased in the HFD group but decreased in the CRD group at 16 weeks (P<0.05). The degree of islet cell autophagy was potentially regulated by the levels of FFA and islet cell insulin and glucagon, which may have been due to the effects of Beclin1/BCL2.     

The Combined Effects of Iron Excess in the Diet and Chromium(III) Supplementation on the Iron and Chromium Status in Female Rats

Inadequate iron supply has significant consequences to health. There are some relations between the metabolism of different trace elements, such as iron, zinc, copper and chromium. However, the direction of these interactions can be antagonistic or synergistic, and it depends on many factors. The aim of the study was to evaluate the combined effects of supplementary of chromium(III) propionate complex (Cr3) with iron excess on the Cr and Fe status in healthy female rats. The 36 healthy female Wistar rats were divided into six experimental groups (six animals in each) with different Fe levels—adequate (45 mg kg^?1—100% RDA) and high (excessive—180 mg kg^?1—400% RDA). At the same time, they were supplemented with Cr(III) at doses of 1, 50 and 500 mg kg^?1 of diet: C1—control (Fe 45 mg kg^?1, Cr 1 mg kg^?1); C50 (Fe 45 mg kg^?1, Cr 50 mg kg^?1); C500 (Fe 45 mg kg^?1, Cr 500 mg kg^?1); H1 (Fe 180 mg kg^?1, Cr 1 mg kg^?1); H50 (Fe 180 mg kg^?1, Cr 50 mg kg^?1); H500 (Fe 180 mg kg^?1, Cr 500 mg kg^?1). The serum iron level and total iron binding capacity (TIBC) were measured with colorimetric methods. The serum ferritin level was measured by means of electrochemiluminescence immunoassay. The serum transferrin level was measured with the ELISA method. Haematological measurements were made with an automated blood analyser. The Cr and Fe tissular levels were measured with the AAS method. The exposure to a high level of Fe(III) alone or in combination with Cr caused Fe accumulation in tissues, especially in the liver and kidneys, but there were no significant changes in the TIBC, transferrin, ferritin concentration in the serum and most haematological parameters. Moreover, the serum, hepatic and renal Cr concentrations decreased. The doses of supplementary Cr(III) given separately or in combination with high level of Fe(III) disturbed the Cr content in the liver and kidneys of healthy female rats. However, they did not change most of the parameters of Fe metabolism, except the Fe kidney concentration. Supplementary Cr3 decreased the renal Fe level in groups with adequate Fe content in the diet. However, the renal Fe levels increased along with a higher Cr level in the diet in groups with high Fe content. The findings proved a relationship between Fe(III) and Cr(III) metabolism in healthy female rats. However, the direction of change varied and depended on relative amounts of these elements in the diet.     

Reduced Pain and Inflammation in Juvenile and Adult Rats Fed a Ketogenic Diet

The ketogenic diet is a high-fat, low-carbohydrate regimen that forces ketone-based rather than glucose-based cellular metabolism. Clinically, maintenance on a ketogenic diet has been proven effective in treating pediatric epilepsy and type II diabetes, and recent basic research provides evidence that ketogenic strategies offer promise in reducing brain injury. Cellular mechanisms hypothesized to be mobilized by ketone metabolism and underlying the success of ketogenic diet therapy, such as reduced reactive oxygen species and increased central adenosine, suggest that the ketolytic metabolism induced by the diet could reduce pain and inflammation. To test the effects of a ketone-based metabolism on pain and inflammation directly, we fed juvenile and adult rats a control diet (standard rodent chow) or ketogenic diet (79% fat) ad libitum for 3–4 weeks. We then quantified hindpaw thermal nociception as a pain measure and complete Freund''s adjuvant-induced local hindpaw swelling and plasma extravasation (fluid movement from the vasculature) as inflammation measures. Independent of age, maintenance on a ketogenic diet reduced the peripheral inflammatory response significantly as measured by paw swelling and plasma extravasation. The ketogenic diet also induced significant thermal hypoalgesia independent of age, shown by increased hindpaw withdrawal latency in the hotplate nociception test. Anti-inflammatory and hypoalgesic diet effects were generally more robust in juveniles. The ketogenic diet elevated plasma ketones similarly in both age groups, but caused slowed body growth only in juveniles. These data suggest that applying a ketogenic diet or exploiting cellular mechanisms associated with ketone-based metabolism offers new therapeutic opportunities for controlling pain and peripheral inflammation, and that such a metabolic strategy may offer significant benefits for children and adults.     

A Comparative Study on the Effects of Excess Iodine and Herbs with Excess Iodine on Thyroid Oxidative Stress in Iodine-Deficient Rats

This study aimed to compare the effect of excess iodine and herbs with excess iodine on treating iodine deficiency-induced goiter from the perspective of oxidative stress and to measure selenium values in Chinese herbs. One hundred twenty 4-week-old Wistar rats were selected and randomly divided into four groups after inducing iodine-deficiency goiter: normal control group (NC), model control group (MC), iodine excess group (IE), and herbs with iodine excess group (HIE). The activities of oxidative enzymes and levels of oxidative products were measured using biochemical tests. The expression of 4-hydroxynonenal (4-HNE) in the thyroid was detected by immunohistochemistry and the expression of peroxiredoxin 5 (PRDX5) by the Western blot and immunohistochemistry. Selenium values in iodine-excessive herbs were measured by hydride generation-atomic fluorescence spectrometry. The herbs with iodine excess were tested to contain rich selenium. The activities of superoxide dismutase (SOD) and PRDX5 increased markedly, and the values of malondialdehyde (MDA) and 4-HNE decreased significantly in the HIE group. In conclusion, compared with excess iodine, herbs with excess iodine damaged thyroid follicular cells less, which may be related to the increase of antioxidant capacity and rich selenium values in iodine-excessive herbs.     

Altered Hypothalamic Signaling and Responses to Food Deprivation in Rats Fed a Low‐Carbohydrate Diet

Objective: To model how consuming a low‐carbohydrate (LC) diet influences food intake and body weight. Research Methods and Procedures: Food intake and body weight were monitored in rats with access to chow (CH), LC‐high‐fat (HF), or HF diets. After 8 weeks, rats received intracerebroventricular injections of a melanocortin agonist (melanotan‐II) and antagonist (SHU9119), and feeding responses were measured. At sacrifice, plasma hormones and hypothalamic expression of mRNA for proopiomelanocortin (POMC), melanocortin‐4 receptor, neuropeptide Y (NPY), and agouti related protein (AgRP) were assessed. A second set of rats had access to diet (chow or LC‐HF) for 4 weeks followed by 24 h food deprivation on two occasions, after which food intake and hypothalamic POMC, NPY, and AgRP mRNA expression were measured. Results: HF rats consumed more food and gained more weight than rats on CH or LC‐HF diets. Despite similar intakes and weight gains, LC‐HF rats had increased adiposity relative to CH rats. LC‐HF rats were more sensitive to melanotan‐II and less sensitive to SHU9119. LC‐HF rats had increased plasma leptin and ghrelin levels and decreased insulin levels, and patterns of NPY and POMC mRNA expression were consistent with those of food‐deprived rats. LC‐HF rats did not show rebound hyperphagia after food deprivation, and levels NPY, POMC, and AgRP mRNA expression were not affected by deprivation. Discussion: Our results demonstrate that an LC diet influences multiple systems involved in the controls of food intake and body weight. These data also suggest that maintenance on an LC‐HF diet affects food intake by reducing compensatory responses to food deprivation.     

Anti-Obesity Effects of Melastoma malabathricum var Alba Linn in Rats Fed with a High-Fat Diet

Obesity is one of the major public health problems worldwide and it is generally associated with many diseases. Although synthetic drugs are available for the treatment of obesity, herbal remedies may provide safe, natural, and cost-effective alternative to synthetic drugs. One example of such drugs is Melastoma malabathricum var Alba Linn (MM). Although several studies have been reported for the pharmacological activities of MM, there is no report on the anti-obesity effect of MM. The aim of the present study is to evaluate the anti-obesity potential of methanolic extract of MM. The anti-obesity effect of MM on rats fed with a high-fat diet was investigated through determination of the changes in body weight, fat weight, organ weights, and blood biochemicals. The animals in this study were divided into three groups: a normal group with a standard diet (N), a control group fed with high-fat diet (C), and a MM treatment group fed with high-fat (HFD + MM) diet for 8 weeks. There was no significant difference in the amount of food intake between control and HFD + MM treatments. These results also suggest that MM does not induce a dislike for the diet due to its smell or taste. The study shows that MM significantly prevented increases in body weight, cholesterol, LDL, HDL, and total lipids that resulted from the high-fat diet. MM also decreased the epididymal fat (E-fat) and retroperitoneal fat (R-fat) weights and phospholipid concentrations induced by the high-fat diet. On the basis of these findings, it was concluded that MM had anti-obesity effects by suppressing body weight gain and abdominal fat formation.KEY WORDS: Anti-obesity, High-fat diet, Melastoma malabathricum var Alba Linn     

Methionine and Serine Synergistically Suppress Hyperhomocysteinemia Induced by Choline Deficiency,but Not by Guanidinoacetic Acid,in Rats Fed a Low Casein Diet

The effects of dietary supplementation with 0.5% methionine, 2.5% serine, or both on hyperhomocysteinemia induced by deprivation of dietary choline or by dietary addition of 0.5% guanidinoacetic acid (GAA) were investigated in rats fed a 10% casein diet. Hyperhomocysteinemia induced by choline deprivation was not suppressed by methionine alone and was only partially suppressed by serine alone, whereas it was completely suppressed by a combination of methionine and serine, suggesting a synergistic effect of methionine and serine. Fatty liver was also completely prevented by the combination of methionine and serine. Compared with methionine alone, the combination of methionine and serine decreased hepatic S-adenosylhomocysteine and homocysteine concentrations and increased hepatic betaine and serine concentrations and betaine-homocysteine S-methyltransferase activity. GAA-induced hyperhomocysteinemia was partially suppressed by methionine alone, but no interacting effect of methionine and serine was detected. In contrast, GAA-induced fatty liver was completely prevented by the combination of methionine and serine. These results indicate that a combination of methionine and serine is effective in suppressing both hyperhomocysteinemia and fatty liver induced by choline deprivation, and that methionine alone is effective in suppressing GAA-induced hyperhomocysteinemia partially.     

Effects of a High-Fat Diet and Strain on Hypothalamic Gene Expression in Rats

Objective: This study was designed to investigate whether dietary fat and genetic background might differentially alter the expression of hypothalamic genes involved in food intake. Research Methods and Procedures: Three-month-old Osborne-Mendel (OM) and S5B/Pl rats were fed either a high-fat or a low-fat diet for 14 days. mRNA for neuropeptide Y (NPY), corticotrophin-releasing hormone, NPY Y-1 receptor and Y-5 receptor, and serotonin 2c (5-HT2c) receptors were measured using Northern blotting or ribonuclease protection assays. Results: OM rats showed an increased expression of NPY and corticotrophin-releasing hormone compared with S5B/Pl rats. The expression of NPY-Y1 and -Y5 receptor mRNA was significantly higher in the hypothalamus of OM rats compared with S5B/Pl rats. The expression of 5HT-2c receptor mRNA was significantly reduced in both strains of rats eating a high-fat diet when compared with the animals eating the low-fat diet. Discussion: These data suggest that over activity of the NPY system may contribute to the development of obesity in OM rats and that expression of the 5HT-2c receptor gene may be modulated by dietary fat.     

Changes in Gut Microbiota in Rats Fed a High Fat Diet Correlate with Obesity-Associated Metabolic Parameters

The gut microbiota is emerging as a new factor in the development of obesity. Many studies have described changes in microbiota composition in response to obesity and high fat diet (HFD) at the phylum level. In this study we used 16s RNA high throughput sequencing on faecal samples from rats chronically fed HFD or control chow (n = 10 per group, 16 weeks) to investigate changes in gut microbiota composition at the species level. 53.17% dissimilarity between groups was observed at the species level. Lactobacillus intestinalis dominated the microbiota in rats under the chow diet. However this species was considerably less abundant in rats fed HFD (P<0.0001), this being compensated by an increase in abundance of propionate/acetate producing species. To further understand the influence of these species on the development of the obese phenotype, we correlated their abundance with metabolic parameters associated with obesity. Of the taxa contributing the most to dissimilarity between groups, 10 presented significant correlations with at least one of the tested parameters, three of them correlated positively with all metabolic parameters: Phascolarctobacterium, Proteus mirabilis and Veillonellaceae, all propionate/acetate producers. Lactobacillus intestinalis was the only species whose abundance was negatively correlated with change in body weight and fat mass. This species decreased drastically in response to HFD, favouring propionate/acetate producing bacterial species whose abundance was strongly correlated with adiposity and deterioration of metabolic factors. Our observations suggest that these species may play a key role in the development of obesity in response to a HFD.     

Serotonin Metabolism and Release in Frontal Cortex of Rats on a Vitamin E-Deficient Diet

Abstract: Rats were fed a control or vitamin E (all- rac -α-tocopheryl acetate)-deficient diet for 3 or 12 weeks. Serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), tryptophan, and α-tocopherol concentrations were determined in the frontal cortex using HPLC. α-Tocopherol concentrations fell significantly to 27% of control values at 12 weeks. Tissue 5-HT, 5-HIAA, and tryptophan concentrations were not significantly altered by the vitamin E-deficient diet at either time point. In vivo microdialysis revealed normal basal and K⁺-stimulated concentrations of 5-HT and 5-HIAA, but extracellular concentrations of tryptophan were significantly decreased after 3 weeks on the vitamin E-deficient diet, which resulted in an increase in the tissue/extracellular ratio and suggested a change in compartmentation. However, after 12 weeks on the deficient diet these values had returned to normal. Results in general indicate that a prolonged and substantial depletion of brain vitamin E can occur without major disturbance of serotonergic function.     

Histomorphometric and Microchemical Characterization of Maturing Dental Enamel in Rats Fed a Boron-Deficient Diet

Few reports are available in the literature on enamel formation under nutritional deficiencies. Thus, we performed a study to determine the effects of boron (B) deficiency on the maturing dental enamel, employing the rat continuously erupting incisor as the experimental model. Male Wistar rats, 21 days old, were used throughout. They were divided into two groups, each containing ten animals: +B (adequate; 3-mg B/kg diet) and ?B (boron deficient; 0.07-mg B/kg diet). The animals were maintained on their respective diets for 14 days and then euthanized. The mandibles were resected, fixed, and processed for embedding in paraffin and/or methyl methacrylate. Oriented histological sections of the continuously erupting incisor were obtained at the level of the mesial root of the first molar, allowing access to the maturation zone of the developing enamel. Dietary treatment did not affect food intake and body weight. Histomorphometric evaluation using undecalcified sections showed a reduction in enamel thickness (hypoplasia), whereas microchemical characterization by energy-dispersive X-ray spectrometry did not reveal alterations in enamel mineralization.     

Native and Non-Native Plants Provide Similar Refuge to Invertebrate Prey,but Less than Artificial Plants

Non-native species introductions are widespread and can affect ecosystem functioning by altering the structure of food webs. Invading plants often modify habitat structure, which may affect the suitability of vegetation as refuge and could thus impact predator-prey dynamics. Yet little is known about how the replacement of native by non-native vegetation affects predator-prey dynamics. We hypothesize that plant refuge provisioning depends on (1) the plant’s native status, (2) plant structural complexity and morphology, (3) predator identity, and (4) prey identity, as well as that (5) structurally similar living and artificial plants provide similar refuge. We used aquatic communities as a model system and compared the refuge provided by plants to macroinvertebrates (Daphnia pulex, Gammarus pulex and damselfly larvae) in three short-term laboratory predation experiments. Plant refuge provisioning differed between plant species, but was generally similar for native (Myriophyllum spicatum, Ceratophyllum demersum, Potamogeton perfoliatus) and non-native plants (Vallisneria spiralis, Myriophyllum heterophyllum, Cabomba caroliniana). However, plant refuge provisioning to macroinvertebrate prey depended primarily on predator (mirror carp: Cyprinus carpio carpio and dragonfly larvae: Anax imperator) and prey identity, while the effects of plant structural complexity were only minor. Contrary to living plants, artificial plant analogues did improve prey survival, particularly with increasing structural complexity and shoot density. As such, plant rigidity, which was high for artificial plants and one of the living plant species evaluated in this study (Ceratophyllum demersum), may interact with structural complexity to play a key role in refuge provisioning to specific prey (Gammarus pulex). Our results demonstrate that replacement of native by structurally similar non-native vegetation is unlikely to greatly affect predator-prey dynamics. We propose that modification of predator-prey interactions through plant invasions only occurs when invading plants radically differ in growth form, density and rigidity compared to native plants.     

Mice Deficient in Proglucagon-Derived Peptides Exhibit Glucose Intolerance on a High-Fat Diet but Are Resistant to Obesity

Homozygous glucagon-GFP knock-in mice (Gcg^gfp/gfp) lack proglucagon derived-peptides including glucagon and GLP-1, and are normoglycemic. We have previously shown that Gcg^gfp/gfp show improved glucose tolerance with enhanced insulin secretion. Here, we studied glucose and energy metabolism in Gcg^gfp/gfp mice fed a high-fat diet (HFD). Male Gcg^gfp/gfp and Gcg^gfp/+ mice were fed either a normal chow diet (NCD) or an HFD for 15–20 weeks. Regardless of the genotype, mice on an HFD showed glucose intolerance, and Gcg^gfp/gfp mice on HFD exhibited impaired insulin secretion whereas Gcg^gfp/+ mice on HFD exhibited increased insulin secretion. A compensatory increase in β-cell mass was observed in Gcg^gfp/+mice on HFD, but not in Gcg^gfp/gfp mice on the same diet. Weight gain was significantly lower in Gcg^gfp/gfp mice than in Gcg^gfp/+mice. Oxygen consumption was enhanced in Gcg^gfp/gfp mice compared to Gcg^gfp/+ mice on an HFD. HFD feeding significantly increased uncoupling protein 1 mRNA expression in brown adipose and inguinal white adipose tissues of Gcg^gfp/gfp mice, but not of Gcg^gfp/+mice. Treatment with the glucagon-like peptide-1 receptor agonist liraglutide (200 mg/kg) improved glucose tolerance in Gcg^gfp/gfp mice and insulin content in Gcg^gfp/gfp and Gcg^gfp/+ mice was similar after liraglutide treatment. Our findings demonstrate that Gcg^gfp/gfp mice develop diabetes upon HFD-feeding in the absence of proglucagon-derived peptides, although they are resistant to diet-induced obesity.     

Effect of a Low-Protein Diet Supplemented with Ketoacids on Skeletal Muscle Atrophy and Autophagy in Rats with Type 2 Diabetic Nephropathy

A low-protein diet supplemented with ketoacids maintains nutritional status in patients with diabetic nephropathy. The activation of autophagy has been shown in the skeletal muscle of diabetic and uremic rats. This study aimed to determine whether a low-protein diet supplemented with ketoacids improves muscle atrophy and decreases the increased autophagy observed in rats with type 2 diabetic nephropathy. In this study, 24-week-old Goto-Kakizaki male rats were randomly divided into groups that received either a normal protein diet (NPD group), a low-protein diet (LPD group) or a low-protein diet supplemented with ketoacids (LPD+KA group) for 24 weeks. Age- and weight-matched Wistar rats served as control animals and received a normal protein diet (control group). We found that protein restriction attenuated proteinuria and decreased blood urea nitrogen and serum creatinine levels. Compared with the NPD and LPD groups, the LPD+KA group showed a delay in body weight loss, an attenuation in soleus muscle mass loss and a decrease of the mean cross-sectional area of soleus muscle fibers. The mRNA and protein expression of autophagy-related genes, such as Beclin-1, LC3B, Bnip3, p62 and Cathepsin L, were increased in the soleus muscle of GK rats fed with NPD compared to Wistar rats. Importantly, LPD resulted in a slight reduction in the expression of autophagy-related genes; however, these differences were not statistically significant. In addition, LPD+KA abolished the upregulation of autophagy-related gene expression. Furthermore, the activation of autophagy in the NPD and LPD groups was confirmed by the appearance of autophagosomes or autolysosomes using electron microscopy, when compared with the Control and LPD+KA groups. Our results showed that LPD+KA abolished the activation of autophagy in skeletal muscle and decreased muscle loss in rats with type 2 diabetic nephropathy.