Constitutive adipocyte mTORC1 activation enhances mitochondrial activity and reduces visceral adiposity in mice.

Mechanistic target of rapamycin complex 1 (mTORC1) loss of function reduces adiposity whereas partial mTORC1 inhibition enhances fat deposition. Herein we evaluated how constitutive mTORC1 activation in adipocytes modulates adiposity in vivo. Mice with constitutive mTORC1 activation in adipocytes induced by tuberous sclerosis complex (Tsc)1 deletion and littermate controls were evaluated for body mass, energy expenditure, glucose and fatty acid metabolism, mitochondrial function, mRNA and protein contents. Adipocyte-specific Tsc1 deletion reduced visceral, but not subcutaneous, fat mass, as well as adipocyte number and diameter, phenotypes that were associated with increased lipolysis, UCP-1 content (browning) and mRNA levels of pro-browning transcriptional factors C/EBPß and ERRα. Adipocyte Tsc1 deletion enhanced mitochondrial oxidative activity, fatty acid oxidation and the expression of PGC-1α and PPARα in both visceral and subcutaneous fat. In brown adipocytes, however, Tsc1 deletion did not affect UCP-1 content and basal respiration. Adipocyte Tsc1 deletion also reduced visceral adiposity and enhanced glucose tolerance, liver and muscle insulin signaling and adiponectin secretion in mice fed with purified low- or high-fat diet. In conclusion, adipocyte-specific Tsc1 deletion enhances mitochondrial activity, induces browning and reduces visceral adiposity in mice.

Glucose and fatty acid metabolism in infarcted heart from streptozotocin-induced diabetic rats after 2 weeks of tissue remodeling.

BACKGROUND: The effects of streptozotocin (STZ)-induced diabetes on heart metabolism and function after myocardial infarction (MI) remodelling were investigated in rats. METHODS: Fifteen days after STZ (50 mg/kg b.w. i.v.) injection, MI was induced by surgical occlusion of the left coronary artery. Two weeks after MI induction, contents of glycogen, ATP, free fatty acids and triacylglycerols (TG) and enzyme activities of glycolysis and Krebs cycle (hexokinase, glucose-6-phosphate dehydrogenase, phosphofructokinase, citrate synthase) and expression of carnitine palmitoyl-CoA transferase I (a key enzyme of mitochondrial fatty acid oxidation) were measured in the left ventricle (LV). Plasma glucose, free fatty acids and triacylglycerol levels were determined. Ejection fraction (EF) and shortening fraction (SF) were also measured by echocardiography. RESULTS: Glycogen and TG contents were increased (p < 0.05) whereas ATP content was decreased in the LV of the non-infarcted diabetic group when compared to the control group (p < 0.05). When compared to infarcted control rats (MI), the diabetic infarcted rats (DI) showed (p < 0.05): increased plasma glucose and TG levels, elevated free fatty acid levels and increased activity of, citrate synthase and decreased ATP levels in the LV. Infarct size was smaller in the DI group when compared to MI rats (p < 0.05), and this was associated with higher EF and SF (p < 0.05). CONCLUSIONS: Systolic function was preserved or recovered more efficiently in the heart from diabetic rats two weeks after MI, possibly due to the high provision of glucose and free fatty acids from both plasma and heart glycogen and triacylglycerol stores.

Palmitoleic acid (n-7) increases white adipocytes GLUT4 content and glucose uptake in association with AMPK activation.

BACKGROUND: Palmitoleic acid was previously shown to improve glucose homeostasis by reducing hepatic glucose production and by enhancing insulin-stimulated glucose uptake in skeletal muscle. Herein we tested the hypothesis that palmitoleic acid positively modulates glucose uptake and metabolism in adipocytes. METHODS: For this, both differentiated 3 T3-L1 cells treated with either palmitoleic acid (16:1n7, 200 µM) or palmitic acid (16:0, 200 µM) for 24 h and primary adipocytes from mice treated with 16:1n7 (300 mg/kg/day) or oleic acid (18:1n9, 300 mg/kg/day) by gavage for 10 days were evaluated for glucose uptake, oxidation, conversion to lactate and incorporation into fatty acids and glycerol components of TAG along with the activity and expression of lipogenic enzymes. RESULTS: Treatment of adipocytes with palmitoleic, but not oleic (in vivo) or palmitic (in vitro) acids, increased basal and insulin-stimulated glucose uptake and GLUT4 mRNA levels and protein content. Along with uptake, palmitoleic acid enhanced glucose oxidation (aerobic glycolysis), conversion to lactate (anaerobic glycolysis) and incorporation into glycerol-TAG, but reduced de novo fatty acid synthesis from glucose and acetate and the activity of lipogenic enzymes glucose 6-phosphate dehydrogenase and ATP-citrate lyase. Importantly, palmitoleic acid induction of adipocyte glucose uptake and metabolism were associated with AMPK activation as evidenced by the increased protein content of phospho(p)Thr172AMPKα, but no changes in pSer473Akt and pThr308Akt. Importantly, such increase in GLUT4 content induced by 16:1n7, was prevented by pharmacological inhibition of AMPK with compound C. CONCLUSIONS: In conclusion, palmitoleic acid increases glucose uptake and the GLUT4 content in association with AMPK activation.

Dynamic Changes in Adiponectin and Resistin Drive Remission of Cardiometabolic Risk Biomarkers in Individuals with Obesity Following Bariatric Surgery.

The remission of obesity-related diseases following bariatric surgery appears to result from the reorganization of metabolic and hormonal pathways involving adipokines. This study aimed to investigate the relationship between changes in body adiposity and serum adipokine levels, as well as the association between variations in adiponectin or resistin levels and cardiometabolic risk blood biomarkers before and after Roux-en-Y gastric bypass. A longitudinal and prospective study was conducted with bariatric surgery patients. Anthropometric, body composition and blood biochemical parameters were measured before and at 2 and 6 months post-surgery. The data were analyzed using ANOVA, Pearson or Spearman correlation, and simple linear regression with a significance level of p < 0.05. Among 36 mostly female patients aged 30 to 39 years, significant reductions in body weight (-26.8%), fat mass (-50%), waist circumference (-18%) and waist-to-height ratio (-22%) were observed post-surgery. Serum adiponectin levels increased (+107%), while resistin (-12.2%), TNF-α (-35%), and PAI-1 (-11.1%) decreased. Glucose, insulin, CRP, cholesterol, LDL-c, triglycerides, and vitamin D also decreased. Waist circumference variation showed a positive correlation with PAI-1 and TNF-α and a negative correlation with adiponectin. The total fat mass showed a positive correlation with PAI-1. Adiponectin variation correlated negatively with glucose, resistin, and CRP but positively with HDL-c. Resistin showed a positive correlation with insulin and CRP. In conclusion, 6 months post-bariatric surgery, reducing abdominal adiposity had a more significant impact on serum adipokine levels than total fat mass. Adiponectin increase and resistin decrease acted as endocrine mediators driving the remission of cardiometabolic risk biomarkers in individuals with obesity following Roux-en-Y gastric bypass.

Nutritional status of women with non-metastatic breast cancer receiving outpatient chemotherapy.

OBJECTIVES: The aim of this study was to evaluate and compare the nutritional status of women with stage I to III breast cancer in the first and third cycles of outpatient chemotherapy and to identify factors associated with it. METHODS: The prospective longitudinal study was conducted at a Reference Hospital for Cancer Care in Brazil and included women aged ≥18 y diagnosed with stage I to III breast cancer receiving outpatient chemotherapy. Assessments were performed during the 1st and 3rd cycles of chemotherapy, including anthropometric measurements, sociodemographic data, clinical information, and quality of life. Nutritional risk was assessed using the NRS-2002. RESULTS: Overweight was predominant in both chemotherapy cycles. Approximately 6.67% and 10% of patients were at nutritional risk in the 1st and 3rd chemotherapy cycles, respectively. Anxiety/depression was prevalent in the 1st chemotherapy cycle and was significantly associated with nutritional risk (P = 0.002). The variables age in cycle 3 and pain/discomfort in cycle 1 (P = 0.049 and P = 0.043, respectively) showed a significant association with nutritional risk. CONCLUSIONS: This study highlights the complex interaction between nutritional status, neuropsychological symptoms, and sociodemographic characteristics in breast cancer patients during chemotherapy, and underscores the need for personalized interventions to improve oncological care.

Palmitoleic acid (n-7) increases white adipocyte lipolysis and lipase content in a PPARα-dependent manner.

We investigated whether palmitoleic acid, a fatty acid that enhances whole body glucose disposal and suppresses hepatic steatosis, modulates triacylglycerol (TAG) metabolism in adipocytes. For this, both differentiated 3T3-L1 cells treated with either palmitoleic acid (16:1n7, 200 µM) or palmitic acid (16:0, 200 µM) for 24 h and primary adipocytes from wild-type or PPARα-deficient mice treated with 16:1n7 (300 mg·kg(-1)·day(-1)) or oleic acid (18:1n9, 300 mg·kg(-1)·day(-1)) by gavage for 10 days were evaluated for lipolysis, TAG, and glycerol 3-phosphate synthesis and gene and protein expression profile. Treatment of differentiated 3T3-L1 cells with 16:1n7, but not 16:0, increased basal and isoproterenol-stimulated lipolysis, mRNA levels of adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) and protein content of ATGL and pSer(660)-HSL. Such increase in lipolysis induced by 16:1n7, which can be prevented by pharmacological inhibition of PPARα, was associated with higher rates of PPARα binding to DNA. In contrast to lipolysis, both 16:1n7 and 16:0 increased fatty acid incorporation into TAG and glycerol 3-phosphate synthesis from glucose without affecting glyceroneogenesis and glycerokinase expression. Corroborating in vitro findings, treatment of wild-type but not PPARα-deficient mice with 16:1n7 increased primary adipocyte basal and stimulated lipolysis and ATGL and HSL mRNA levels. In contrast to lipolysis, however, 16:1n7 treatment increased fatty acid incorporation into TAG and glycerol 3-phosphate synthesis from glucose in both wild-type and PPARα-deficient mice. In conclusion, palmitoleic acid increases adipocyte lipolysis and lipases by a mechanism that requires a functional PPARα.

Palmitoleic Acid Acts on Adipose-Derived Stromal Cells and Promotes Anti-Hypertrophic and Anti-Inflammatory Effects in Obese Mice.

Adipose tissue (AT) secretes adipokines, modulators of low-grade chronic inflammation in obesity. Molecules that induce the emergence of new and functional adipocytes in AT can alleviate or prevent inflammatory and metabolic disorders. The objective of this study was to investigate the role of palmitoleic acid (n7) in 3T3-L1 and primary pre-adipocyte differentiation and AT inflammation. C57BL/6j mice were submitted to a control or high-fat diet (HFD) for 8 weeks, and treated with n7 for 4 weeks. Mice consuming a HFD presented an increase in body weight, epididymal (Epi) fat mass, and Epi adipocytes size. N7 treatment attenuated the body weight gain and completely prevented the hypertrophy of Epi adipocytes, but not the increment in Epi mass induced by the HFD, suggesting a greater adipocytes hyperplasia in animals treated with n7. It was agreed that n7 increased 3T3-L1 proliferation and differentiation, as well as the expression of genes involved in adipogenesis, such as Cebpa, Pparg, aP2, Perilipin, and Scl2a4. Furthermore, n7 decreased the inflammatory cytokines Mcp1, Tnfa, Il6, Cxcl10, and Nos2 genes in Epi vascular stromal cells, but not in the whole AT. These findings show that n7 exerts anti-hypertrophic effects in adipocytes which influence the surrounding cells by attenuating the overexpression of pro-inflammatory cytokines triggered by a HFD.

Obesity and covid-19: a reflection on the relationship between pandemics.

OBJECTIVE: Carry out a reflective analysis on the relationship of obesity as a risk factor for the worsening of COVID-19. METHOD: Reflective study, supported by scientific evidence, which contributed to a critical-reflexive construction on the theme "Obesity" in interface with "Covid-19". RESULTS: This study brought up important reflections for health professionals, researchers and managers, from the beginning of the pandemic, a period in which obesity was not recognized as a risk factor, until the current scenario, in which a series of pathophysiological mechanisms that clinically connect these diseases are being proposed. CONCLUSION: Obesity is a risk factor for the worsening of COVID-19, which is contributing to the overload of health services, and which requires differentiated health care, with adjustments in care, pharmacological protocols and commitment to health education in the within the Unified Health System.

Lipolysis and lipases in white adipose tissue - An update.

Lipolysis is defined as the sequential hydrolysis of triacylglycerol (TAG) stored in cell lipid droplets. For many years, it was believed that hormone-sensitive lipase (HSL) and monoacylglycerol lipase (MGL) were the main enzymes catalyzing lipolysis in the white adipose tissue. Since the discovery of adipose triglyceride lipase (ATGL) in 2004, many studies were performed to investigate and characterize the actions of this lipase, as well as of other proteins and possible regulatory mechanisms involved, which reformulated the concept of lipolysis. Novel findings from these studies include the identification of lipolytic products as signaling molecules regulating important metabolic processes in many non-adipose tissues, unveiling a previously underestimated aspect of lipolysis. Thus, we present here an updated review of concepts and regulation of white adipocyte lipolysis with a special emphasis in its role in metabolism homeostasis and as a source of important signaling molecules.

Regulation of brown adipose tissue recruitment, metabolism and thermogenic function by peroxisome proliferator-activated receptor γ.

Brown adipose tissue contributes importantly to homeothermy and energy balance in rodents due its ability under demand to produce heat through a process denominated nonshivering thermogenesis. Such thermogenic ability of brown adipocytes relies on the activity of mitochondrial uncoupling protein 1 that, when properly activated, dissipates energy from oxidative metabolism as heat. Brown adipose tissue sympathetic innervation through norepinephrine release not only induces brown adipocyte lipolysis and thermogenesis, but also acts as the major determinant of tissue mass, cellularity and mitochondrial content. Several pieces of evidence gathered over the years indicate that, in addition to tissue sympathetic innervation, the nuclear receptor peroxisome proliferator-activated receptor γ plays an important role in regulating the development, metabolism and thermogenic function of brown adipose tissue. Herein we review the main evidence supporting such key role of peroxisome proliferator-activated receptor γ to brown fat biology and discuss the future directions of this important area of research.

Risco de Infecção e Motilidade Gastrintestinal Disfuncional: diagnósticos mais frequentes no pós-operatório de cirurgia bariátrica / Risk of infection and dysfunctional gastrointestinal motility: most frequent diagnostics in the post-operatory of bariatric surgery

Objetivo: Identificar os sinais e sintomas clínicos e os diagnósticos de enfermagem mais frequentes em pacientes no pós-operatório imediato de cirurgia bariátrica. Metodologia: Estudo observacional. A coleta de dados foi realizada por dois examinadores e contemplou a caracterização epidemiológica, social, clínica e exame físico. A presença e a frequência dos sinais e sintomas clínicos foram registradas e propiciaram a elaboração dos diagnósticos de enfermagem, segundo a taxonomia NANDA-I 2018-2020. Resultados: Participaram 50 pacientes, sendo predominantemente do sexo feminino, faixa etária entre 30-39 anos e renda mensal de 1,0 a 1,5 salários. E 80% dos pacientes relatam possuir histórico familiar de obesidade. Foram levantados os 16 sinais e sintomas clínicos e os 16 diagnósticos de enfermagem mais frequentes, com destaque para os títulos diagnósticos: riscos de infecção e motilidade gastrointestinal disfuncional. Conclusão: O presente trabalho identificou os sinais e sintomas e os diagnósticos de enfermagem mais frequentes de pacientes no pós-operatório imediato de cirurgia bariátrica, além de realizar o levantamento de importantes dados sociodemográficos, epidemiológicos e da história clínica. Esses achados favorecem a implantação do processo de enfermagem através da facilitação do raciocínio diagnóstico do enfermeiro. (AU)

Objective: To identify the most frequent clinical signs and symptoms and nursing diagnoses in patients in the immediate postoperative period of bariatric surgery. Methods: Observational study. Data collection was performed by two examiners and included epidemiological, social, clinical and physical examination. The presence and frequency of clinical signs and symptoms were recorded and led to the development of nursing diagnoses, according to the NANDA-I taxonomy 2018-2020. Results: 50 patients participated, being predominantly female, aged between 30-39 years and monthly income of 1.0 to 1.5 salaries. 80% of patients report having a family history of obesity. The 16 most frequent clinical signs and symptoms and the 16 nursing diagnoses were raised, with emphasis on the diagnostic titles: risks of infection and dysfunctional gastrointestinal motility. Conclusion: The present study identified the most frequent nursing signs and symptoms and also nursing diagnoses of patients in the immediate postoperative period of bariatric surgery, in addition to surveying important sociodemographic, epidemiological and clinical history data. These findings favor the implementation of the nursing process by facilitating the nurse's diagnostic reasoning. (AU)

Objetivo: identificar los signos y síntomas clínicos más comunes y los diagnósticos de enfermería en pacientes en el postoperatorio inmediato de cirugía bariátrica. Métodos: estudio observacional. La recopilación de datos fue realizada por dos examinadores e incluyó un examen epidemiológico, social, clínico y físico. La presencia y frecuencia de signos y síntomas clínicos se registraron y condujeron al desarrollo de diagnósticos de enfermería, según la taxonomía NANDA-I 2018-2020. Resultados: participaron 50 pacientes, predominantemente mujeres, con edades entre 30-39 años e ingresos mensuales de 1.0 a 1.5 salarios. Y el 80% de los pacientes informan tener antecedentes familiares de obesidad. Se plantearon los 16 signos y síntomas clínicos más frecuentes y los 16 diagnósticos de enfermería, con énfasis en los títulos de diagnóstico: riesgos de infección y motilidad gastrointestinal disfuncional. Conclusión: El presente estudio identificó los signos y síntomas de enfermería más frecuentes y los diagnósticos de enfermería de pacientes en el postoperatorio inmediato de cirugía bariátrica, además de encuestar datos importantes de historia sociodemográfica, epidemiológica y clínica. Estos hallazgos favorecen la implementación del proceso de enfermería al facilitar el razonamiento diagnóstico de la enfermera. (AU)

Lipolysis and lipases in white adipose tissue – An update

Lipolysis is defined as the sequential hydrolysis of triacylglycerol (TAG) stored in cell lipid droplets. For many years, it was believed that hormone-sensitive lipase (HSL) and monoacylglycerol lipase (MGL) were the main enzymes catalyzing lipolysis in the white adipose tissue. Since the discovery of adipose triglyceride lipase (ATGL) in 2004, many studies were performed to investigate and characterize the actions of this lipase, as well as of other proteins and possible regulatory mechanisms involved, which reformulated the concept of lipolysis. Novel findings from these studies include the identification of lipolytic products as signaling molecules regulating important metabolic processes in many non-adipose tissues, unveiling a previously underestimated aspect of lipolysis. Thus, we present here an updated review of concepts and regulation of white adipocyte lipolysis with a special emphasis in its role in metabolism homeostasis and as a source of important signaling molecules.