Sulforaphane reduces pro-inflammatory response to palmitic acid in monocytes and adipose tissue macrophages.

Chronic low-grade systemic inflammation (SI), including activation of the NLRP3 inflammasome, is a feature of obesity, associated with increased circulating saturated fatty acids, such as palmitic acid (PA), and bacterial endotoxin lipopolysaccharide (LPS). PA and LPS may contribute to SI observed in obesity, while the dietary antioxidant sulforaphane has been shown to reduce activation of the NLRP3 inflammasome. This study investigated immune cell responses from obese subjects to PA, and the effects of sulforaphane on NLRP3 activation/inflammation. Peripheral blood monocytes isolated from obese (n = 8) and non-obese (n = 8) subjects and adipose tissue macrophages (ATMs) isolated from visceral fat obtained from obese subjects (n = 10) during bariatric surgery were pre-treated with/without sulforaphane (40 µM) for 3 hours then stimulated with PA (500 µM) ± LPS (1 ng/mL monocytes; 100 ng/mL ATMs) for 15 hours. Culture supernatants were assessed for tumor necrosis factor-α and interleukin-ß (IL-1ß) by enzyme-linked immunosorbent assay, NLRP3 inflammasome gene expression was assessed by quantitative polymerase chain reaction, IL-1ß and NLRP3 expression were higher in both unstimulated and PA treated monocytes from obese compared to nonobese subjects. In ATMs neither PA alone or combined with LPS increased cytokine production or inflammasome gene expression. Sulforaphane reduced tumor necrosis factor-α and IL-1ß from monocytes in both groups, however inflammasome associated genes were only reduced in monocytes from obese subjects. Sulforaphane reduced cytokine production and inflammasome gene expression in ATMs. NLRP3 inflammasome activation by PA is higher in obesity, which maybe driven by baseline activation of the NLRP3 inflammasome. Sulforaphane modulates inflammatory responses in immune cells and may play a role in reducing SI in obesity.

Weight Loss and Short-Chain Fatty Acids Reduce Systemic Inflammation in Monocytes and Adipose Tissue Macrophages from Obese Subjects.

BACKGROUND: Chronic low-grade systemic inflammation is a characteristic of obesity that leads to various non-communicable diseases. Weight loss and SCFAs are potential strategies for attenuating obese systemic inflammation. METHODS: Blood samples were collected from 43 obese subjects (BMI ≥ 30 kg/m2) scheduled for laparoscopic bariatric sleeve surgery, 26 obese subjects at follow-up 12-18 months post-surgery and 8 healthy weight subjects (BMI 18.5-24.9 kg/m2). Monocytes were isolated from blood and adipose tissue macrophages from visceral adipose tissue of obese subjects only. Isolated cells stimulated with 1 ng/mL LPS and treated simultaneously with 300 mM of sodium acetate or 30 mM of sodium propionate or butyrate and supernatant were harvested after 15 h incubation. TNF-α and IL-6 cytokines were measured via ELISA and mRNA gene expression of FFAR2 and FFAR3, HDAC1, HDAC2 and HDAC9, RELA and NFKB1 and MAPK1 via RT-qPCR. RESULTS: TNF-α and IL-6 production and NFKB1 and RELA mRNA expression were significantly decreased in follow-up subjects compared to baseline. SCFAs significantly reduced TNF-α and IL-6 and altered FFAR and HDAC mRNA expression in monocytes and macrophages from obese subjects. CONCLUSION: Weight loss and ex vivo SCFA treatments were successful in combatting systemic inflammation in obesity. Results highlighted molecular changes that occur with weight loss and as a result of SCFA treatment.

Identifying conservation successes, failures and future opportunities; assessing recovery potential of wild ungulates and tigers in Eastern Cambodia.

Conservation investment, particularly for charismatic and wide-ranging large mammal species, needs to be evidence-based. Despite the prevalence of this theme within the literature, examples of robust data being generated to guide conservation policy and funding decisions are rare. We present the first published case-study of tiger conservation in Indochina, from a site where an evidence-based approach has been implemented for this iconic predator and its prey. Despite the persistence of extensive areas of habitat, Indochina's tiger and ungulate prey populations are widely supposed to have precipitously declined in recent decades. The Seima Protection Forest (SPF), and broader Eastern Plains Landscape, was identified in 2000 as representing Cambodia's best hope for tiger recovery; reflected in its designation as a Global Priority Tiger Conservation Landscape. Since 2005 distance sampling, camera-trapping and detection-dog surveys have been employed to assess the recovery potential of ungulate and tiger populations in SPF. Our results show that while conservation efforts have ensured that small but regionally significant populations of larger ungulates persist, and density trends in smaller ungulates are stable, overall ungulate populations remain well below theoretical carrying capacity. Extensive field surveys failed to yield any evidence of tiger, and we contend that there is no longer a resident population within the SPF. This local extirpation is believed to be primarily attributable to two decades of intensive hunting; but importantly, prey densities are also currently below the level necessary to support a viable tiger population. Based on these results and similar findings from neighbouring sites, Eastern Cambodia does not currently constitute a Tiger Source Site nor meet the criteria of a Global Priority Tiger Landscape. However, SPF retains global importance for many other elements of biodiversity. It retains high regional importance for ungulate populations and potentially in the future for Indochinese tigers, given adequate prey and protection.