Maternal and Sex Dependency of Insulin Resistance: Longitudinal PET and Echocardiography Study from the Healthy Fetus to the Adult Minipig

n/

Developmental ORIgins of Healthy and Unhealthy AgeiNg : The Role of Maternal Obesity - Introduction to DORIAN

Peer reviewe

A Qualitative Exploration of the Use of Contraband Cell Phones in Secured Facilities

Offenders accepting contraband cell phones in secured facilities violate state corrections law, and the possession of these cell phones is a form of risk taking behavior. When offenders continue this risky behavior, it affects their decision making in other domains where they are challenging authorities; and may impact the length of their incarceration. This qualitative phenomenological study examined the lived experience of ex-offenders who had contraband cell phones in secured correctional facilities in order to better understand their reasons for taking risks with contraband cell phones. The theoretical foundation for this study was Trimpop\u27s risk-homeostasis and risk-motivation theories that suggest an individual\u27s behaviors adapt to negotiate between perceived risk and desired risk in order to achieve satisfaction. The research question explored beliefs and perceptions of ex-offenders who chose to accept the risk of using contraband cell phones during their time in secured facilities. Data were collected anonymously through recorded telephone interviews with 8 male adult ex-offenders and analyzed using thematic content analysis. Findings indicated participants felt empowered by possession of cell phones in prison, and it was an acceptable risk to stay connected to family out of concern for loved ones. The study contributes to social change by providing those justice system administrators, and prison managers responsible for prison cell phone policies with more detailed information about the motivations and perspectives of offenders in respect to using contraband cell phones while imprisoned in secured facilities

Metabolismo d'organo nell'obesita e nel diabete di tipo2. Studio nel piccolo animale con tomografia ad emissione di positroni

RIASSUNTO Questo progetto è volto alla valutazione dei meccanismi di tossicità metabolica indotti da obesità, iperglicemia acuta ed iperglicemia cronica e del possibile coinvolgimento di quest’ultima nello sviluppo di steatosi d’organo. Il progetto, diviso in due studi, è stato eseguito nel piccolo animale utilizzando la Tomografia ad Emissione di Positroni (PET) come principale strumento di indagine del metabolismo d’organo in vivo. METODI. Nel primo studio sono stati utilizzati ratti Wistar, sottoposti ad esame PET con ammoniaca marcata con 13N (13NH3) e 11C-acetato durante digiuno (n=5) o iperglicemia acutamente indotta (n=4) e successivamente sacrificati per l’espianto degli organi. I dati di cinetica tessutale dei traccianti sono stati utilizzati per quantificare perfusione e de novo lipogenesi a livello d’organo. Gli indici di de novo lipogenesi sono stati validati per confronto con la proporzione di tracciante misurata nella frazione organica di ciascun tessuto. La procedura PET è stata estesa a 8 ratti Zucker/ZDF, obesi e/o diabetici per valutare gli effetti della malattia. Nel secondo studio sono stati utilizzati ratti Zucker/ZDF, di cui 10 con obesità, 10 con diabete di tipo 2, 15 di controllo, sottoposti ad esame PET con [13N]NH3 e 18F-FDG durante digiuno o iperglicemia acuta. Dall’analisi delle immagini è stato caratterizzato il flusso ed metabolismo d’organo di ciascun tipo di malattia. RISULTATI. Negli animali di controllo, l’iperglicemia acuta causava un aumento di flusso sanguigno rispetto al digiuno a livello dei tessuti epatico, muscolare ed adiposo. Questa risposta risultava assente nel tessuto adiposo degli animali obesi, e nel fegato e nel muscolo degli animali diabetici. Il flusso miocardico era marginalmente stimolato dall’iperglicemia negli animali sani, e ridotto negli animali diabetici. Negli animali sani, l’utilizzazione tessutale del glucosio aumentava significativamente di circa tre volte durante iperglicemia acuta rispetto ai valori a digiuno. Questi ultimi erano più alti in tutti i tessuto degli animali affetti da obesità e diabete, presentando una variazione non significativa durante stimolo nel muscolo, cuore e tessuto adiposo. Nel fegato l’utilizzazione di glucosio era persistentemente aumentata. La de novo lipogenesi tessutale veniva rapidamente attivata a seguito di stimolo glucidico acuto negli animali sani; in presenza di insulino-resistenza, essendo già elevata in condizioni di digiuno, essa non manifestava alcun tipo di regolazione acuta. CONCLUSIONI. Con l’utilizzo di una metodica diretta e non invasiva, abbiamo evidenziato la relazione esistente fra utilizzazione di glucosio, perfusione e lipogenesi, a livello d’organo, documentando che l’iperglicemia, l’obesità ed il diabete modificano questi processi. In particolare, le due malattie metaboliche mostrano un aumento della utilizzazione di substrati a digiuno ed una riduzione tessuto specifica della risposta perfusionale e metabolica ad uno stimolo iperglicemico simile a quello post-prandiale. Concludiamo che una continua sovraesposizione tessutale al glucosio e l’assenza di flessibilità metabolica promuovono l’accumulo tessutale di substrato, portando ad una glucotossicità associata alla attivazione cronica della de novo lipogenesi. ABSTRACT This project addresses the mechanisms of metabolic toxicity induced by obesity, acute and chronic hyperglycaemia, and the potential involvement of the latter in the development of organ steatosis. The project was divided in two studies and it was carried out in small animals, by using Positron Emission Tomography as main tool for the investigation of organ metabolism in vivo. METHODS. In the first study, 9 Wistar rats underwent PET imaging with 13N-labelled ammonia (NH3) e 11C-acetate during fasting (n=5) or acutely induced hyperglycaemia (n=4), at the end of which they were sacrificed for organ explantation. Tracer tissue kinetics data were used to quantify organ perfusion (13NH3) and de novo lipogenesis (11C-acetate). Indexes of de novo lipogenesis were validated by comparison with the proportion of tracer recovered ex-vivo in the organic fraction in each tissue. The PET imaging procedure was used in 8 obese and/or diabetic Zucker/ZDF rats to evaluate the effects of disease. The second study included 10 obese, 10 type 2 diabetic and 15 control Zucker/ZDF rats, undergoing PET imaging with 13NH3 e 18F-labelled fluorodeoxyglucose during fasting or acute hyperglycaemia. Image analyses were performed to characterize organ perfusion and glucose metabolism in each metabolic disease. RESULTS. In control animals, acute hyperglycaemia caused an increase in hepatic, skeletal muscle and adipose tissue blood flow over fasting values. This response was not observed in the adipose tissue of obese rats, and in the liver and muscle in diabetic animals. Myocardial blood flow was only marginally up-regulated by hyperglycaemia in healthy animals, and it was defective in diabetic rats. In control animals, tissue glucose utilization underwent a significant, approximately threefold rise during acute hyperglycaemia as compared with fasting values. The latter were higher in all tissues in both diabetic and obese rats; in the muscle, heart and fat, they showed a non significant variation during acute glucose stimulation. In the liver, glucose uptake was persistently elevated. Tissue de novo lipogenesis underwent rapid activation following acute glucose stimulation in healthy animals; in insulin-resistant rats, it was already elevated during fasting conditions and showed no acute regulation. CONCLUSIONS. By using a direct and non-invasive molecular imaging technique, we have described the relationship between organ specific glucose utilization, perfusion, and lipogenesis, documenting that acute hyperglycaemia, obesity and diabetes modify these processes. In particular, the two metabolic disorders show an increase in substrate metabolism during fasting conditions, and a tissue-specific reduction in the flow and metabolic response to an acute hyperglycaemic stimulus, mimicking a post-prandial condition. We conclude that a persistent overexposure to glucose and absent metabolic flexibility promote tissue accumulation of substrate, leading to glucose toxicity associated with a chronic activation in de novo lipogenesis

Brain glucose overexposure and lack of acute metabolic flexibility in obesity and type 2 diabetes: a PET-[18F]FDG study in Zucker and ZDF rats

Brain glucose exposure may complicate diabetes and obesity. We used positron emission tomography with 18F-fluorodeoxyglucose in Zucker obese, diabetic, and control rats to determine the contributions of blood glucose mass action versus local mechanisms in regulating central glucose disposal in fasted and acutely glucose-stimulated states, and their adaptations in obesity and diabetes. Our study data indicate that brain glucose uptake is dependent on both local and mass action components, and is stimulated by acute glucose intake in healthy rats. In diseased animals, the organ was chronically overexposed to glucose, due to high fasting glucose uptake, almost abolishing the physiologic response to glucose loading

Impact of obesity on the expression profile of natriuretic peptide system in a rat experimental model.

Natriuretic peptides (NPs) play an important role in obesity and aim of this study was to evaluate, in cardiac tissue of obese Zucker rats (O, n = 29) their transcriptomic profile compared to controls (CO, n = 24) by Real-Time PCR study; CNP protein expression was evaluated by immunostaining and immunometric tests. Myocardial histology was performed, confirming no alteration of organ structure. While ANP and BNP are cardiac peptides, CNP is mainly an endothelial hormone; thus its expression, as well as that of NPR-B and NPR-C, was also evaluated in kidney and lung of an animal subgroup (n = 20). In heart, lower BNP mRNA levels in O vs CO (p = 0.02) as well as ANP and CNP (p = ns), were detected. NPR-B/NPR-A mRNA was similar in O and CO, while NPR-C was numerically lower (p = ns) in O than in CO. In kidney, CNP/NPR-B/NPR-C mRNA was similar in O and CO, while in lung CNP/NPR-C expression decreased and NPR-B increased (p = ns) in O vs CO. Subdividing into fasting and hyperglycemic rats, the pattern of mRNA expression for each gene analyzed remained unchanged. The trend observed in heart, kidney and lung for CNP protein concentrations and immunohistochemistry reflected the mRNA expression. TNF-α and IL-6 mRNA were measured in each tissue and no significant genotype effect was detected in any tissue. The main NP variations were observed at the cardiac level, suggesting a reduced release by cardiac cells. The understanding of mechanisms involved in the modulation of the NP system in obesity could be a useful starting point for future clinical study devoted to identifying new obesity treatment strategies

mRNA expression of a) BNP, b) ANP, c) CNP, d) NPR-B, e) NPR-A and f) NPR-C in cardiac tissue of control lean (CO, white bar) and obese Zucker rats (O, black bar).

<p>mRNA expression of a) BNP, b) ANP, c) CNP, d) NPR-B, e) NPR-A and f) NPR-C in cardiac tissue of control lean (CO, white bar) and obese Zucker rats (O, black bar).</p

CNP, NPR-B and NPR-C mRNA expression in renal and pulmonary tissue of control lean (CO, white bar) and obese Zucker rats (O, black bar).

<p>On the left side: <b>a)</b> CNP, <b>b)</b> NPR-B, <b>c)</b> NPR-C relative levels in kidney. On the right side: <b>d)</b> CNP, <b>e)</b> NPR-B, <b>f)</b> NPR-C relative levels in lung.</p

Details of specific primers used in Real-Time PCR experiments.

<p><b>Legend: Sdha:</b> Succinate dehydrogenase complex, subunit A, flavoprotein; <b>Hprt1:</b> Hypoxanthine phosphoribosyltransferase 1; <b>Tbp:</b> TATA binding protein; <b>ANP:</b> atrial natriuretic peptide; <b>BNP:</b> B-type (or brain) natriuretic peptide; <b>CNP:</b> C-type natriuretic peptide; <b>NPR-A:</b> Natriuretic peptide receptor A; <b>NPR-B:</b> Natriuretic peptide receptor B; <b>NPR-C:</b> Natriuretic peptide receptor C or clearance receptor; <b>IL-6:</b> Interleukin-6; <b>TNF-α:</b> Tumor necrosis factor-alpha.</p

Representative hematoxylin/eosin staining from heart sections of controland obese rats.

<p><b>Scale bar: 50 µm.</b></p