Krüppel-like factor 3 (KLF3) is a transcriptional regulator that we have shown to be involved in the regulation of adipogenesis in vitro. Here, we report that KLF3-null mice are lean and protected from diet-induced obesity and glucose intolerance. On a chow diet, plasma levels of leptin are decreased, and adiponectin is increased. Despite significant reductions in body weight and adiposity, wild-type and knockout animals show equivalent energy intake, expenditure, and excretion. To investigate the molecular events underlying these observations, we used microarray analysis to compare gene expression in Klf3+/+ and Klf3−/− tissues. We found that mRNA expression of Fam132a, which encodes a newly identified insulin-sensitizing adipokine, adipolin, is significantly upregulated in the absence of KLF3. We confirmed that KLF3 binds the Fam132a promoter in vitro and in vivo and that this leads to repression of promoter activity. Further, plasma adipolin levels were significantly increased in Klf3−/− mice compared with wild-type littermates. Boosting levels of adipolin via targeting of KLF3 offers a novel potential therapeutic strategy for the treatment of insulin resistance.

The conversion of white adipocytes to thermogenic beige adipocytes represents a potential mechanism to treat obesity and related metabolic disorders. However, the mechanisms involved in converting white to beige adipose tissue remain incompletely understood. Here we show profound beiging in a genetic mouse model lacking the transcriptional repressor Krüppel-like factor 3 (KLF3). Bone marrow transplants from these animals confer the beige phenotype on wild type recipients. Analysis of the cellular and molecular changes reveal an accumulation of eosinophils in adipose tissue. We examine the transcriptomic profile of adipose-resident eosinophils and posit that KLF3 regulates adipose tissue function via transcriptional control of secreted molecules linked to beiging. Furthermore, we provide evidence that eosinophils may directly act on adipocytes to drive beiging and highlight the critical role of these little-understood immune cells in thermogenesis.

The Lgals3 gene encodes a multifunctional ␤-galactosidebinding protein, galectin-3. Galectin-3 has been implicated in a broad range of biological processes from chemotaxis and inflammation to fibrosis and apoptosis. The role of galectin-3 as a modulator of inflammation has been studied intensively, and recent evidence suggests that it may serve as a protective factor in obesity and other metabolic disorders. Despite considerable interest in galectin-3, little is known about its physiological regulation at the transcriptional level. Here, using knockout mice, chromatin immunoprecipitations, and cellular and molecular analyses, we show that the zinc finger transcription factor Krüp-pel-like factor 3 (KLF3) directly represses galectin-3 transcription. We find that galectin-3 is broadly up-regulated in KLF3-deficient mouse tissues, that KLF3 occupies regulatory regions of the Lgals3 gene, and that KLF3 directly binds its cognate elements (CACCC boxes) in the galectin-3 promoter and represses its activation in cellular assays. We also provide mechanistic insights into the regulation of Lgals3, demonstrating that C-terminal binding protein (CtBP) is required to drive optimal KLF3-mediated silencing. These findings help to enhance our understanding of how expression of the inflammatory modulator galectin-3 is controlled, opening up avenues for potential therapeutic interventions in the future.

Anacardium occidentale Linn. (A. occidentale L.) leaves possess bioactive polyphenols which are associated with antidiabetic potency for the management of type 2 diabetes mellitus (T2DM). In this study, free, soluble ester, and insoluble-bound phenolic fractions from young and mature leaves of A. occidentale L. were extracted. Subsequently, all fractions were investigated for their inhibitory effect on α-amylase and dipeptidyl peptidase IV (DPPIV) activities. Both free (72.45 ± 3.6%) and soluble ester (83.40 ± 4.7%) phenolic fractions in the mature leaves extracts had significantly demonstrated greater α-amylase inhibitors than the young leaves. Likewise, soluble ester (4.09 ± 0.34 µg/mL) and insoluble-bound (4.87 ± 0.32 µg/mL) phenolic fractions in the mature leaves extracts were significantly more effective in inhibiting DPPIV than the young leaves. As for fractions comparison, insoluble-bound derived from the young leaves extract was a more potent α-amylase inhibitor than free and soluble ester phenolic fractions (p < 0.0001). Besides, soluble ester and insoluble-bound phenolic fractions showed a stronger inhibitor of DPPIV than the free phenolic (p < 0.001), irrespective of the maturity of the leaves. In conclusion, this study showed that A. occidentale L. extracts possessed antidiabetic properties, which may potentially be used as an alternative treatment for T2DM management.

Despite growing evidence of increased saturated and trans fat contents in street foods, little is known about their fatty acid (FA) compositions. This study aimed to analyse the saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), polyunsaturated fatty acids (PUFAs), and trans fatty acids (TFAs) content of 70 selected and most commonly available street foods in Malaysia. The street foods were categorised into main meals, snacks, and desserts. TFAs were not detected in any of the street foods. Descriptively, all three categories mainly contained SFAs, followed by MUFAs, and PUFAs. However, the one-way ANOVA testing showed that the differences between each category were insignificant (p > 0.05), and each FA was not significantly different (p > 0.05) from one to another. Nearly half of the deep-fried street foods contained medium to high SFAs content (1.7 g/100 g–24.3 g/100 g), while the MUFAs were also high (32.0–44.4%). The Chi-square test of association showed that the type of preparation methods (low or high fat) used was significantly associated (p < 0.05) with the number of SFAs. These findings provide valuable information about fat composition in local street foods for the Malaysian Food Composition Database and highlight the urgency to improve nutritional composition.