BACKGROUND:Metabolic syndrome (METS) is an increasingly prevalent but poorly understood clinical condition characterized by insulin resistance, glucose intolerance, dyslipidemia, hypertension, and obesity. Increased oxidative stress catalyzed by accumulation of iron in excess of physiologic requirements has been implicated in the pathogenesis of METS, but the relationships between cause and effect remain uncertain. We tested the hypothesis that phlebotomy-induced reduction of body iron stores would alter the clinical presentation of METS, using a randomized trial.

METHODS:In a randomized, controlled, single-blind clinical trial, 64 patients with METS were randomly assigned to iron reduction by phlebotomy (n = 33) or to a control group (n = 31), which was offered phlebotomy at the end of the study (waiting-list design). The iron-reduction patients had 300 ml of blood removed at entry and between 250 and 500 ml removed after 4 weeks, depending on ferritin levels at study entry. Primary outcomes were change in systolic blood pressure (SBP) and insulin sensitivity as measured by Homeostatic Model Assessment (HOMA) index after 6 weeks. Secondary outcomes included HbA1c, plasma glucose, blood lipids, and heart rate (HR).

RESULTS:SBP decreased from 148.5± 12.3 mmHg to 130.5 ± 11.8 mmHg in the phlebotomy group, and from 144.7 ± 14.4 mmHg to 143.8 ± 11.9 mmHg in the control group (difference -16.6 mmHg; 95% CI -20.7 to -12.5; P<0.001). No significant effect on HOMA index was seen. With regard to secondary outcomes, blood glucose, HbA1c, low-density lipoprotein/high-density lipoprotein ratio, and HR were significantly decreased by phlebotomy. Changes in BP and HOMA index correlated with ferritin reduction.

CONCLUSIONS:In patients with METS, phlebotomy, with consecutive reduction of body iron stores, lowered BP and resulted in improvements in markers of cardiovascular risk and glycemic control. Blood donation may have beneficial effects for blood donors with METS.

TRIAL REGISTRATION:ClinicalTrials.gov: NCT01328210 Please see related article: http://www.biomedcentral.com/1741-7015/10/53.

A two-arm randomized open labeled controlled clinical trial was conducted on 50 patients with non-alcoholic fatty liver disease (NAFLD). Participants were assigned to take either a lifestyle modification (LM), or LM +30 g/day brown milled flaxseed for 12 weeks. At the end of the study, body weight, liver enzymes, insulin resistance and hepatic fibrosis and steatosis decreased significantly in both groups (p< 0.05); however, this reduction was significantly greater in those who took flaxseed supplementation (p < 0.05). The significant mean differences were reached in hepatic markers between flaxseed and control group, respectively: ALT [-11.12 compared with -3.7 U/L; P< 0.001], AST [-8.29 compared with -4 U/L; p< 0.001], GGT [-15.7 compared with -2.62 U/L; p < 0.001], fibrosis score [-1.26 compared with -0.77 kPa; p = 0.013] and steatosis score [-47 compared with -15.45 dB/m; p = 0.022]. In conclusion, flaxseed supplementation plus lifestyle modification is more effective than lifestyle modification alone for NAFLD management.

A two-arm randomized open labeled controlled clinical trial was conducted on 50 patients with non-alcoholic fatty liver disease (NAFLD). Participants were assigned to take either a lifestyle modification (LM), or LM +30 g/day brown milled flaxseed for 12 weeks. At the end of the study, body weight, liver enzymes, insulin resistance and hepatic fibrosis and steatosis decreased significantly in both groups (p< 0.05); however, this reduction was significantly greater in those who took flaxseed supplementation (p < 0.05). The significant mean differences were reached in hepatic markers between flaxseed and control group, respectively: ALT [-11.12 compared with -3.7 U/L; P< 0.001], AST [-8.29 compared with -4 U/L; p< 0.001], GGT [-15.7 compared with -2.62 U/L; p < 0.001], fibrosis score [-1.26 compared with -0.77 kPa; p = 0.013] and steatosis score [-47 compared with -15.45 dB/m; p = 0.022]. In conclusion, flaxseed supplementation plus lifestyle modification is more effective than lifestyle modification alone for NAFLD management.

AIM:To examine whether low circulating vitamin C concentrations and low fruit and vegetable intakes were associated with insulin resistance and other Type 2 diabetes risk markers in childhood.

METHODS:We conducted a cross-sectional, school-based study in 2025 UK children aged 9-10 years, predominantly of white European, South-Asian and black African origin. A 24-h dietary recall was used to assess fruit, vegetable and vitamin C intakes. Height, weight and fat mass were measured and a fasting blood sample collected to measure plasma vitamin C concentrations and Type 2 diabetes risk markers.

RESULTS:In analyses adjusting for confounding variables (including socio-economic status), a one interquartile range higher plasma vitamin C concentration (30.9μmol/l) was associated with a 9.6% (95% CI 6.5, 12.6%) lower homeostatic model assessment of insulin resistance value, 0.8% (95% CI 0.4, 1.2%) lower fasting glucose, 4.5% (95% CI 3.2, 5.9%) lower urate and 2.2% (95% CI 0.9, 3.4%) higher HDL cholesterol. HbA1c concentration was 0.6% (95% CI 0.2, 1.0%) higher. Dietary fruit, vegetable and total vitamin C intakes were not associated with any Type 2 diabetes risk markers. Lower plasma vitamin C concentrations in South-Asian and black African-Caribbean children could partly explain their higher insulin resistance.

CONCLUSIONS:Lower plasma vitamin C concentrations are associated with insulin resistance and could partly explain ethnic differences in insulin resistance. Experimental studies are needed to establish whether increasing plasma vitamin C can help prevent Type 2 diabetes at an early stage. This article is protected by copyright. All rights reserved.

BACKGROUND:We have shown that individually, dietary fiber and protein increase secretion of the anorexigenic and insulinotropic hormone, glucagon-like peptide-1 (GLP-1).

OBJECTIVE:Our objective was to combine, in one diet, high levels of fiber and protein to maximize GLP-1 secretion, improve glucose tolerance, and reduce weight gain.

METHODS AND PROCEDURES:Lean (+/?) and obese (cp/cp) male James C Russell corpulent (JCR:LA-cp) rats lacking a functional leptin receptor were fed one of four experimental diets (control, high protein (HP), high fiber (HF, prebiotic fiber inulin), or combination (CB)) for 3 weeks. An oral glucose tolerance test (OGTT) was performed to evaluate plasma GLP-1, insulin and glucose. Plasma lipids and intestinal proglucagon mRNA expression were determined.

RESULTS:Energy intake was lower with the HF diet in lean and obese rats. Weight gain did not differ between diets. Higher colonic proglucagon mRNA in lean rats fed a CB diet was associated with higher GLP-1 secretion during OGTT. The HP diet significantly reduced plasma glucose area under the curve (AUC) during OGTT in obese rats, which reflected both an increased GLP-1 AUC and higher fasting insulin. Diets containing inulin resulted in the lowest plasma triglyceride and total cholesterol levels.

DISCUSSION:Overall, combining HP with HF in the diet increased GLP-1 secretion in response to oral glucose, but did not improve glucose tolerance or lipid profiles more than the HF diet alone did. We also suggest that glycemic and insulinemic response to prebiotics differ among rat models and future research work should examine their role in improving glucose tolerance in diet-induced vs. genetic obesity with overt hyperleptinemia.

The development of obesity is cornerstone in the etiology of metabolic and vascular insulin resistance and consequently exacerbates glycemic control. Exercise is an efficacious first-line therapy for type 2 diabetes that improves insulin action through, in part, reducing hormone mediated inflammation. Together, improving the coordination of skeletal muscle metabolism with vascular delivery of glucose will be required for optimizing type 2 diabetes and cardiovascular disease treatment.

BACKGROUND:The gastrointestinal tract (GIT) harbors a complex and diverse microbial composition that outnumbers our own body cells and their gene contents. These microbes play a significant role in host metabolism and energy homeostasis. Emerging evidence suggests that the GIT microbiome significantly contributes to host health and that impairments in the microbiome may cause the development of metabolic diseases. The microbiome architecture is shaped by several genetic and environmental factors, including nutrition and physical activity. Physical exercise has preventive or therapeutic effects in respiratory, cardiovascular, neuroendocrine, and muscular diseases. Yet, we still have little information of the beneficial effects of physical exercise on GIT health and microbial composition. Furthermore, we are not aware whether exercise-derived benefits on microbiome diversity can beneficially influence other tissues and body organs.

OBJECTIVES:The aim of this article is to review the available literature on exercise-induced microbiome changes and to explain how these changes may induce inflammatory, immune, and oxidative responses that may contribute to the improvement of metabolic disorders.

METHODS:A systemic and comprehensive search of the relevant literature using MEDLINE and Google Scholar databases was conducted during fall 2018 and spring 2019. The search identified sixty-two research and review articles that discussed exercise-induced microbiome changes.

RESULTS:The review of the relevant literature suggests that exercise-induced microbial changes affect the host's immune pathways and improve energy homeostasis. Microbes release certain neuroendocrine and immune-modulatory factors that may lower inflammatory and oxidative stress and relieve patients suffering from metabolic disorders.

CONCLUSIONS:Exercise-induced changes in microbial diversity are able to improve tissue metabolism, cardiorespiratory fitness, and insulin resistance.

BACKGROUND:Urtica dioica (UD) has been identified as a traditional herbal medicine. This study aimed to investigate the effect of UD extract and swimming activity on diabetic parameters through in vivo and in vitro experiments.

METHODS:Adult WKY male rats were randomly distributed in nine groups: intact control, diabetic control, diabetic + 625 mg/kg, 1.25 g/kg UD, diabetic + 100 mg/kg Metformin, diabetic + swimming, diabetic + swimming 625 mg/kg, 1.25 g/kg UD, and diabetic +100 mg/kg Metformin + swimming. The hearts of the animals were punctured, and blood samples were collected for biochemical analysis. The entire pancreas was exposed for histologic examination. The effect of UD on insulin secretion by RIN-5F cells in 6.25 or 12.5 mM glucose dose was examined. Glucose uptake by cultured L6 myotubes was determined.

RESULTS:The serum glucose concentration decreased, the insulin resistance and insulin sensitivity significantly increased in treated groups. These changes were more pronounced in the group that received UD extract and swimming training. Regeneration and less beta cell damage of Langerhans islets were observed in the treated groups. UD treatment increased insulin secretion in the RIN-5F cells and glucose uptake in the L6 myotubes cells.

CONCLUSIONS:Swimming exercises accompanied by consuming UD aqueous extracts effectively improved diabetic parameters, repaired pancreatic tissues in streptozotocin-induced diabetics in vivo, and increased glucose uptake or insulin in UD-treated cells in vitro.

AIM:- To determine whether exercise training improves insulin actions through concomitant body weight loss (BWL).

METHODS:- Subjects (aged 55± 8 years) with metabolic syndrome (MetS), prediabetes (fasting blood glucose: 111 ± 2 mg·dL, HbA1c: 5.85± 0.05%) and abdominal obesity (waist circumference: 104 ± 7.9 cm) were randomly allocated to either a group performing aerobic interval training (EXER; n = 76) or a sedentary group receiving lifestyle counselling (CONT; n = 20) for 16 weeks. Results - At baseline, insulin sensitivity (according to HOMA2 and intravenous glucose tolerance test; CS), body composition and VOwere similar between the groups. After the intervention, both groups had similar BWL (1-2%), but only the EXER group showed decreased [mean (95% CI)] trunk fat mass [from 18.2 (17.4-18.9) to 17.3 kg (16.6-17.9); P<0.001] and HOMA2 scores [from 1.6 (1.5-1.7) to 1.4 (1.3-1.5); P = 0.001], and increased VO[from 2.07 (1.92-2.21) to 2.28 (2.11-2.45) LO·min; P<0.001]. However, CSdid not improve in any group. Within-group subdivision by BWL (≤ 0%, 0-3%, ≥ 3%) revealed higher CSin those with BWL≥ 3% in both groups. Trunk fat mass reductions were closely associated with CSand HOMA-IR improvement (r = -0.452-0.349; P<0.001).

CONCLUSION:- In obese MetS subjects with prediabetes, 3% BWL is required for consistent improvement in insulin sensitivity. Thus, exercise-training programmes should be combined with calorie restriction to achieve BWL levels that prevent the development of diabetes.

Obesity-induced diabetes is characterized by hyperglycemia, insulin resistance, and progressive beta cell failure. In islets of mice with obesity-induced diabetes, we observe increased beta cell death and impaired autophagic flux. We hypothesized that intermittent fasting, a clinically sustainable therapeutic strategy, stimulates autophagic flux to ameliorate obesity-induced diabetes. Our data show that despite continued high-fat intake, intermittent fasting restores autophagic flux in islets and improves glucose tolerance by enhancing glucose-stimulated insulin secretion, beta cell survival, and nuclear expression of NEUROG3, a marker of pancreatic regeneration. In contrast, intermittent fasting does not rescue beta-cell death or induce NEUROG3 expression in obese mice with lysosomal dysfunction secondary to deficiency of the lysosomal membrane protein, LAMP2 or haplo-insufficiency of BECN1/Beclin-1, a protein critical for autophagosome formation. Moreover, intermittent fasting is sufficient to provoke beta cell death in non-obese lamp2 null mice, attesting to a critical role for lysosome function in beta cell homeostasis under fasting conditions. Beta cells in intermittently-fasted LAMP2- or BECN1-deficient mice exhibit markers of autophagic failure with accumulation of damaged mitochondria and upregulation of oxidative stress. Thus, intermittent fasting preserves organelle quality via the autophagy-lysosome pathway to enhance beta cell survival and stimulates markers of regeneration in obesity-induced diabetes.

This study aimed to evaluate the clinical efficacy of acupuncture for intervening insulin resistance (IR) by meta-analysis of related randomized controlled trials (RCTs). Studies published prior to 31 January 2018 were searched on Pubmed, Medline, Cochrane Library, Embase databases and Chinese databases. Only RCTs, which examined acupuncture as the sole or adjunctive treatment for IR-related diseases, were included. The primary outcome was homeostasis model assessment for insulin resistance (HOMA-IR). The secondary outcomes consisted of fasting blood glucose (FBG), fasting insulin (FINS) and 2-h postprandial blood glucose (2h-PBG). The differences between groups were reported as mean differences (MD). All statistical analyses were performed using RevMan software 5.3. After carefully screening relevant studies, 9 RCTs involving 562 patients (279 in experimental group and 283 in control group) were enrolled in this study. The pooled results showed that acupuncture had significant effects on HOMA-IR (MD 0.70, 95% CI 0.04 to 1.35, P=0.04<0.05), FINS (MD 3.35 mU/L, 95% CI 1.99 to 4.7, P<0.001) and 2h-PBG (MD 1.03 mmol/L, 95% CI 0.25 to 1.82, P=0.01). However, the differences in FBG were not significant (MD 0.28 mmol/L, 95% CI-0.28 to 0.84, P=0.32>0.05). The present meta-analysis indicated that acupuncture can help to improve IR to a certain extent, which remains to be confirmed by further high-quality RCTs.

The lemon detox program is a very low-calorie diet which consists of a mixture of organic maple and palm syrups, and lemon juice for abstinence period of 7 days. We hypothesized that the lemon detox program would reduce body weight, body fat mass, thus lowering insulin resistance and known risk factors of cardiovascular disease. We investigated anthropometric indices, insulin sensitivity, levels of serum adipokines, and inflammatory markers in overweight Korean women before and after clinical intervention trial. Eighty-four premenopausal women were randomly divided into 3 groups: a control group without diet restriction (Normal-C), a pair-fed placebo diet group (Positive-C), and a lemon detox diet group (Lemon-D). The intervention period was 11 days total: 7 days with the lemon detox juice or the placebo juice, and then 4 days with transitioning food. Changes in body weight, body mass index, percentage body fat, and waist-hip ratio were significantly greater in the Lemon-D and Positive-C groups compared to the Normal-C group. Serum insulin level, homeostasis model assessment insulin resistance scores, leptin, and adiponectin levels decreased in the Lemon-D and Positive-C groups. Serum high-sensitive C-reactive protein (hs-CRP) levels were also reduced only in the Lemon-D group. Hemoglobin and hematocrit levels remained stable in the Lemon-D group while they decreased in the Positive-C and Normal-C groups. Therefore, we suppose that the lemon detox program reduces body fat and insulin resistance through caloric restriction and might have a potential beneficial effect on risk factors for cardiovascular disease related to circulating hs-CRP reduction without hematological changes.

Calorie restriction is a dietary intervention known to improve redox state, glucose tolerance, and animal life span. Other interventions have been adopted as study models for caloric restriction, including nonsupplemented food restriction and intermittent, every-other-day feedings. We compared the short- and long-term effects of these interventions to ad libitum protocols and found that, although all restricted diets decrease body weight, intermittent feeding did not decrease intra-abdominal adiposity. Short-term calorie restriction and intermittent feeding presented similar results relative to glucose tolerance. Surprisingly, long-term intermittent feeding promoted glucose intolerance, without a loss in insulin receptor phosphorylation. Intermittent feeding substantially increased insulin receptor nitration in both intra-abdominal adipose tissue and muscle, a modification associated with receptor inactivation. All restricted diets enhanced nitric oxide synthase levels in the insulin-responsive adipose tissue and skeletal muscle. However, whereas calorie restriction improved tissue redox state, food restriction and intermittent feedings did not. In fact, long-term intermittent feeding resulted in largely enhanced tissue release of oxidants. Overall, our results show that restricted diets are significantly different in their effects on glucose tolerance and redox state when adopted long-term. Furthermore, we show that intermittent feeding can lead to oxidative insulin receptor inactivation and glucose intolerance.

The cornerstone to treat metabolic syndrome and insulin resistance is dietary intervention. Both low-carbohydrate diet (LCD) and low-fat diet (LFD) have been reported to induce weight loss and improve these conditions. One of the factors associated with a subject's adherence to the diet is satiety. The aim of this study was to evaluate the effects of LCD and LFD on body weight, appetite hormones, and insulin resistance. Twenty guinea pigs were randomly assigned to LCD or LFD (60%:10%:30% or 20%:55%:25% of energy from fat/carbohydrate/protein, respectively) for 12 weeks. Weight and food intake were recorded every week. After this period, animals were killed and plasma was obtained to measure plasma glucose and insulin, appetite hormones, and ketone bodies. Guinea pigs fed LCD gained more weight than those fed LFD. The daily amount of food intake in grams was not different between groups, suggesting that food density and gastric distension played a role in satiety. There was no difference in leptin levels, which excludes the hypothesis of leptin resistance in the LCD group. However, plasma glucagon-like peptide-1 was 47.1% lower in animals fed LCD (P<.05). Plasma glucose, plasma insulin, and insulin sensitivity were not different between groups. However, the heavier animals that were fed LFD had impairment in insulin sensitivity, which was not observed in those fed LCD. These findings suggest that satiety was dependent on the amount of food ingested. The weight gain in animals fed LCD may be related to their greater caloric intake, lower levels of glucagon-like peptide-1, and higher protein consumption. The adoption of LCD promotes a unique metabolic state that prevents insulin resistance, even in guinea pigs that gained more weight. The association between weight gain and insulin resistance seems to be dependent on high carbohydrate intake.

Low-intensity swimming training, started at an early age, was undertaken to observe glycemic control in hypothalamic obese mice produced by neonatal monosodium l-glutamate (MSG) treatment. Although swimming exercises by weaning pups inhibited hypothalamic obesity onset and recovered sympathoadrenal axis activity, this event was not observed when exercise training is applied to young adult mice. However, the mechanisms producing this improved metabolism are still not fully understood. Current work verifies whether, besides reducing fat tissue accumulation, low-intensity swimming in MSG-weaned mice also improves glycemic control. Although MSG and control mice swam for 15 min/day, 3 days a week, from the weaning stage up to 90 days old, sedentary MSG and normal mice did not exercise at all. After 14 h of fasting, animals were killed at 90 days of age. Retroperitonial fat accumulation was measured to estimate obesity. Fasting blood glucose and insulin concentrations were also measured. Mice were also submitted to ipGTT. MSG obese mice showed fasting hyperglycemia, hyperinsulinemia, and glucose intolerance and insulin resistance. However, the exercise was able to block MSG treatment effects. Higher total cholesterol and triglycerides observed in MSG mice were normalized by exercise after weaning. Exercised MSG animals had higher HDLc than the sedentary group. Data suggest that early exercise training maintains normoglycemia, insulin tissue sensitivity, and normal lipid profile in mice programmed to develop metabolic syndrome.

The present study was undertaken to analyze the acute and chronic effects of exercise on insulin sensitivity in elder diabetic patients using a horseback riding therapeutic equipment (Joba). The acute effects of exercise were examined by means of a single session of Joba riding that lasted for 30 min. The average glucose infusion rates (GIR) before and during exercise were regarded as an index of the insulin action in peripheral tissues by the euglycemic clamp. The chronic effects of exercise were studied by training the elder diabetic patients for 12 weeks using the Joba apparatus. The insulin sensitivity was determined pre- and post-training by a 90 min euglycemic clamp. In the acute study, average GIR during exercise was significantly higher than pre-exercise (7.8+/-0.4 versus 5.2+/-0.3 mg kg(-1)min(-1), P<0.01) and average GIR during recovery decreased to almost the same levels of pre-exercise (5.0+/-0.4 mg kg(-1)min(-1); P<0.01). The 12-week training resulted in a significant increase in the steady-state GIR (from 5.2+/-0.3 to 7.4+/-0.8 mg kg(-1)min(-1); P<0.05). The steady-state GIR after 12 weeks of detraining returned to pre-training levels (5.3+/-0.5 mg kg(-1)min(-1); P<0.05). In elder diabetic patients, mechanical horseback riding enhances the insulin-induced glucose uptake.

Caloric restriction rapidly reverses type 2 diabetes (T2D), but the mechanism(s) of this reversal are poorly understood. Here we show that 3 days of a very-low-calorie diet (VLCD, one-quarter their typical intake) lowered plasma glucose and insulin concentrations in a rat model of T2D without altering body weight. The lower plasma glucose was associated with a 30% reduction in hepatic glucose production resulting from suppression of both gluconeogenesis from pyruvate carboxylase (VPC), explained by a reduction in hepatic acetyl-CoA content, and net hepatic glycogenolysis. In addition, VLCD resulted in reductions in hepatic triglyceride and diacylglycerol content and PKCɛ translocation, associated with improved hepatic insulin sensitivity. Taken together, these data show that there are pleotropic mechanisms by which VLCD reverses hyperglycemia in a rat model of T2D, including reduced DAG-PKCɛ-induced hepatic insulin resistance, reduced hepatic glycogenolysis, and reduced hepatic acetyl-CoA content, PC flux, and gluconeogenesis.

BACKGROUND: The benefit of the Mediterranean-style dietary pattern in mitigating metabolic risk factors for type 2 diabetes and cardiovascular disease has not been well investigated among nondiabetic Americans.

OBJECTIVE: The aim of this study was to examine the prospective association between the Mediterranean-style dietary pattern and metabolic syndrome.

DESIGN: The Mediterranean-style dietary pattern score (MSDPS) was used to characterize a Mediterranean-style dietary pattern in the Framingham Heart Study Offspring Cohort. We examined the longitudinal association between MSDPS and metabolic syndrome traits (including homeostasis model assessment-insulin resistance, fasting glucose, waist circumference, triglyceride, HDL cholesterol, and systolic and diastolic blood pressure) among 2730 participants of the Framingham Heart Study Offspring Cohort without type 2 diabetes (baseline median age: 54 y; 55% women), who were followed from the fifth (baseline) to the seventh study examinations (mean follow-up time: 7 y), and metabolic syndrome incidence (according to the National Cholesterol Education Program Adult Treatment Panel III definition) in 1918 participants free of the condition at baseline.

RESULTS: A higher MSDPS was associated with lower homeostasis model assessment-insulin resistance (P = 0.02), waist circumference (P<0.001), fasting plasma glucose (P = 0.03), and triglycerides (P<0.001) and higher HDL cholesterol (P = 0.02) after adjustment for the corresponding baseline values and for several confounding factors associated with type 2 diabetes risk. Participants in the highest quintile category of the MSDPS had a lower incidence of metabolic syndrome than those in the lowest quintile category (38.5% compared with 30.1%; P = 0.01).

CONCLUSION: Our study suggests that the consumption of a diet consistent with the principles of the Mediterranean-style diet may protect against metabolic syndrome in Americans.

A sustained elevation of glucocorticoid production, associated with the establishment of insulin resistance (IR) could add to the deleterious effects of the IR state. The aim of this study is to analyze the consequences of long-term feeding with a sucrose-rich diet (SRD) on Pomc/ACTH production, define the underlying cellular processes, and determine the effects of moderate exercise (ME) on these parameters. Animals fed a standard chow with or without 30% sucrose in the drinking water were subjected to ME. Circulating hormone levels were determined, and pituitary tissues were processed and analyzed by immunobloting and quantitative real-time PCR. Parameters of oxidative stress (OxS), endoplasmic reticulum stress, and autophagy were also determined. Rats fed SRD developed a decrease in pituitary Pomc/ACTH expression levels, increased expression of antioxidant enzymes, and induction of endoplasmic reticulum stress and autophagy. ME prevented pituitary dysfunction as well as induction of antioxidant enzymes and autophagy. Reporter assays were performed in AtT-20 corticotroph cells incubated in the presence of palmitic acid. Pomc transcription was inhibited by palmitic acid-dependent induction of OxS and autophagy, as judged by the effect of activators and inhibitors of both processes. Long-term feeding with SRD triggers the generation of OxS and autophagy in the pituitary gland, which could lead to a decline in Pomc/ACTH/glucocorticoid production. These effects could be attributed to an increase in fatty acids availability to the pituitary gland. ME was able to prevent these alterations, suggesting additional beneficial effects of ME as a therapeutic strategy in the management of IR.