Cis-9, Trans-11 Conjugated Linoleic Acid Reduces Phosphoenolpyruvate Carboxykinase Expression and Hepatic Glucose Production in HepG2 Cells.

Dysregulated hepatic gluconeogenesis is a hallmark of insulin resistance and type 2 diabetes mellitus (T2DM). Although existing drugs have been proven to improve gluconeogenesis, achieving this objective with functional food is of interest, especially using conjugated linoleic acid (CLA) found in dairy products. Both cis-9, trans-11 (c9,t11) and trans-10, cis-12 (t10,c12) isomers of CLA were tested in human (HepG2) and rat (H4IIE) hepatocytes for their potential effects on gluconeogenesis. The hepatocytes exposed for 24 h with 20 µM of c9,t11-CLA had attenuated the gluconeogenesis in both HepG2 and H4IIE by 62.5% and 80.1%, respectively. In contrast, t10,c12-CLA had no effect. Of note, in HepG2 cells, the exposure of c9,t11-CLA decreased the transcription of gluconeogenic enzymes, cytosolic phosphoenolpyruvate carboxykinase (PCK1) by 87.7%, and glucose-6-phosphatase catalytic subunit (G6PC) by 38.0%, while t10,c12-CLA increased the expression of G6PC, suggesting the isomer-specific effects of CLA on hepatic glucose production. In HepG2, the peroxisome proliferator-activated receptor (PPAR) agonist, rosiglitazone, reduced the glucose production by 72.9%. However, co-administration of c9,t11-CLA and rosiglitazone neither exacerbated nor attenuated the efficacy of rosiglitazone to inhibit glucose production; meanwhile, t10,c12-CLA abrogated the efficacy of rosiglitazone. Paradoxically, PPARγ antagonist GW 9662 also led to 70.2% reduction of glucose production and near undetectable PCK1 expression by abrogating CLA actions. Together, while the precise mechanisms by which CLA isomers modulate hepatic gluconeogenesis directly or via PPAR warrant further investigation, our findings establish that c9,t11-CLA suppresses gluconeogenesis by decreasing PEPCK on hepatocytes.

Effect of 95% Ethanol Khat Extract and Cathinone on in vitro Human Recombinant Cytochrome P450 (CYP) 2C9, CYP2D6, and CYP3A4 Activity.

BACKGROUND AND OBJECTIVE: A significant number of people worldwide consume khat on daily basis. Long term of khat chewing has shown negative impact on several organ systems. It is likely that these people are co-administered khat preparations and conventional medication, which may lead to khat-drug interactions. This study aimed to reveal the inhibitory potencies of khat ethanol extract (KEE) and its major active ingredient (cathinone) on human cytochrome P450 (CYP) 2C9, CYP2D6, and CYP3A4 enzymes activities, which are collectively responsible for metabolizing 70-80% clinically used drugs. METHODS: In vitro fluorescence-based enzyme assays were developed and the CYP enzyme activities were quantified in the presence and absence of KEE and cathinone employing Vivid® CYP450 Screening Kits. RESULTS: KEE inhibited human CYP2C9, CYP2D6, and CYP3A4 enzyme activities with IC50 of 42, 62, and 18 µg/ml. On the other hand, cathinone showed negligible inhibitory effect on these CYPs. Further experiments with KEE revealed that KEE inhibited CYP2C9 via non-competitive or mixed mode with Ki of 14.7 µg/ml, CYP2D6 through competitive or mixed mode with Ki of 17.6 µg/ml, CYP3A4 by mixed inhibition mode with Ki of 12.1 µg/ml. CONCLUSION: Khat-drug interactions are possible due to administration of clinical drugs metabolized by CYP2C9/CYP2D6/CYP3A4 together with khat chewing. Further in vivo studies are required to confirm our findings and identify the causative constituents of these inhibitory effects.

Adverse health effects and unhealthy behaviors among medical students using Facebook.

Little is known about the relationships between adverse health effects and unhealthy behaviors among medical students using Facebook. The aim of this study was to determine the associations between adverse health effects and unhealthy behaviors with Facebook use. A cross-sectional study was conducted in a private university in Malaysia among 316 medical students. A self-administered questionnaire was used. It included questions on sociodemographics, pattern of Facebook use, social relationship, unhealthy behaviors, and health effects. Mean age was 20.5 (±2.7) years. All students had a Facebook account. The average daily Facebook surfing hours were 2.5 (±1.7). Significant associations were found between average hours of Facebook surfing and the following factors: isolation from family members and community, refusing to answer calls, musculoskeletal pain, headache, and eye irritation (P < 0.005). The average hours spent on Facebook were significantly associated with holding urination and defecation while online, surfing Facebook until midnight, and postponing, forgetting, or skipping meals (P < 0.005). The average hours spent on Facebook were associated with adverse health effects and unhealthy behaviors among medical students, as well as social isolation from the family and community.