Present methods to screen for alcohol abuse are generally obtrusive and result in referral to services that deal mainly with alcoholics. These factors deter physicians from identifying alcohol abuse patients at an early stage. In the present study, 81% of all primary care physicians of a single city evaluated (i) the efficiency and the acceptability of a nonobtrusive screening method for the identification of problem drinkers and (ii) the effectiveness of brief cognitive behavioral counseling given by a nurse in a lifestyle context. Patients (n = 15,686) attending the private practices of 42 primary-care physicians were asked four alcohol-neutral trauma questions in the reception area. Physicians asked about alcohol use and alcohol-related problems only to patients with previous trauma. Problem drinkers by defined criteria were offered an appointment with a nurse who, by random assignment, gave either 3-hr of cognitive behavioral counseling over 1 year or simply advised patients to reduce their alcohol intake. The screening method identified 62-85% of expected number of problem drinkers in this population. Following the application of exclusion criteria, 105 problem drinkers were entered in the intervention part of the study. After 1 year, patients who received counseling showed significant reductions in reported alcohol consumption (-70%; p < 0.001), psychosocial problems (-85%; p < 0.001) and serum gamma glutamyl transferase (-32% to -58%; p < 0.02). Physician visits were reduced (-34%; p < 0.02) following counseling. Patients receiving only advice showed neither reductions in psychosocial problems nor in serum gamma glutamyl transferase or physician visits, but reported a 46% reduction (p < 0.01) in alcohol consumption. Data indicate that asking patients about recent trauma is efficient and is well accepted as the first screening instrument in the identification of the problem drinker. Cost of screening per patient is under one dollar. Counseling of 3 hr given by a nurse is markedly superior (p < 0.05) to simple advice in reducing alcohol consumption, objective indicators of alcohol-related morbidity, and the frequency of physician visits.

Inflammatory adipokines secreted from adipose tissue are major contributors to obesity-associated inflammation and other metabolic dysfunctions. We and others have recently documented the contribution of adipose tissue renin-angiotensin system to the pathogenesis of obesity, inflammation, and insulin resistance. We hypothesized that adipocyte-derived angiotensinogen (Agt) plays a critical role in adipogenesis and/or lipogenesis as well as inflammation. This was tested using 3T3-L1 adipocytes, stably transfected with Agt-shRNA or scrambled Sc-shRNA as a control. Transfected preadipocytes were differentiated and used to investigate the role of adipose Agt through microarray and PCR analyses and adipokine profiling. As expected, Agt gene silencing significantly reduced the expression of Agt and its hormone product angiotensin II (Ang II), as well as lipid accumulation in 3T3-L1 adipocytes. Microarray studies identified several genes involved in lipid metabolism and inflammatory pathways which were down-regulated by Agt gene inactivation, such as glycerol-3-phosphate dehydrogenase 1 (Gpd1), serum amyloid A 3 (Saa3), nucleotide-binding oligomerization domain containing 1 (Nod1), and signal transducer and activator of transcription 1 (Stat1). Mouse adipogenesis PCR arrays revealed lower expression levels of adipogenic/lipogenic genes such as peroxisome proliferator activated receptor gamma (PPARγ), sterol regulatory element binding transcription factor 1 (Srebf1), adipogenin (Adig), and fatty acid binding protein 4 (Fabp4). Further, silencing of Agt gene significantly lowered expression of pro-inflammatory adipokines including interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and monocyte chemotactic protein-1 (MCP-1). In conclusion, this study directly demonstrates critical effects of Agt in adipocyte metabolism and inflammation and further support a potential role for adipose Agt in the pathogenesis of obesity-associated metabolic alterations.

Angiotensinogen (Agt), the only known precursor for the hypertensive hormone Angiotensin II (Ang II), is expressed in adipose tissue. Studies from our laboratory and others have provided evidence linking adipocyte‐derived Agt to obesity, inflammation and insulin resistance. To further determine the direct contribution of adipose Agt to these disorders, we generated 3T3‐L1 cells stably transfected with Agt‐shRNA or scrambled‐shRNA sequences, to determine changes in metabolic and inflammatory markers as well as global transcriptional alterations caused by Agt silencing. Adipocytes lacking Agt exhibited significantly reduced levels of Ang II, triglycerides and lipogenic gene expression, consistent with decreased PPAR‐γ activity. Knockdown of the Agt gene also downregulated several adipose tissue inflammatory markers including IL6, TNF‐α and MCP‐1. Furthermore, microarray and qRT‐PCR analyses revealed several candidate genes involved in lipid metabolism and inflammatory pathways, which were differentially regulated by Agt; these included NOD1, a novel Pattern Recognition Receptor, the acute phase protein SAA3, the transcription factor STAT1 and the chemokine CXCL12, all of which were down regulated by Agt silencing. In conclusion, our findings suggest that adipose Agt plays a critical role in adipose tissue expansion and the associated inflammation and metabolic complications.Grant Funding Source: UT Obesity Research Center and TN AgResearch

In this study, we investigated the effects of eicosapentaenoic acid (EPA) on prevention (P) and reversal (R) of high‐fat (HF) diet‐induced obesity and metabolic alterations. Male C57BL/6J mice were fed low‐fat (LF), HF or a HF‐EPA‐P diet for 11 weeks. A fourth group was initially fed HF for 6 weeks followed by HF‐EPA‐R diet for 5 weeks. As expected, mice fed HF diet developed obesity and glucose intolerance. In contrast, mice fed HF‐EPA‐P diet maintained normal glucose tolerance despite weight gain when compared to the LF group. While the HF group developed fasting hyperglycemia and hyperinsulinemia, both HF‐EPA groups (P and R)‐R exhibited normal glycemia and insulinemia, demonstrating EPA's ability to prevent and improve insulin resistance associated with high fat feeding. Analysis of adipokines revealed that plasma adiponectin levels were lower in the HF group, but were comparable between LF and HF‐EPA groups, regardless of the high fat content of the diet. Further analysis of adipose tissue adipokine levels and proteomic studies in cultured adipocytes demonstrated that EPA reduces adipose inflammation (MCP‐1 and PAI‐1) and lipogenesis, while increasing fatty acid oxidation and mitochondrial content. These studies demonstrate that beneficial effects of EPA in improving insulin resistance are in part mediated by EPA's lipid oxidizing and anti‐inflammatory effects.Grant Funding Source: UT‐ORC, AHA and USDA‐NRI