Associations between CD36 gene polymorphisms, fat tolerance and oral fat preference in a young-adult population.

BACKGROUND/OBJECTIVES: CD36 is known to be an orosensory receptor for dietary long-chain fatty acids, as well as being involved in the chemosensory mechanisms within the human gut. Recent data have demonstrated an association between CD36 single-nucleotide polymorphisms (SNPs) and lipid consumption behaviours in humans. This study aimed to test for associations between CD36 SNPs and response to a high-fat meal in a young healthy Australian cohort. Secondary associations were tested between CD36 gene variants and fasting lipid parameters, body composition, cardiovascular disease (CVD) risk factors and measures of oral fat preference. SUBJECTS/METHODS: Two SNPs (rs1527479 and rs1984112) were assessed for associations with response to a 75 g saturated fat oral fat tolerance test (OFTT), whole-body substrate oxidation, fasting plasma lipids, CVD risk factors and self-reported habitual diet questionnaires. Genotyping was performed using real-time polymerase chain reaction. RESULTS: Cross-sectional data were collected on 56 individuals (28 m, 28 f; 24.9±3.3 years), with 42 completing participation in a high-fat OFTT. No genotypic associations were evident in anthropometric data or self-reported fat preference measures. AA SNP carriers at rs1984112 exhibited significantly elevated fasting triglyceride when compared with non-carriers (P=0.024). This group also tended to have an elevated response to a high-fat meal (P=0.078). CONCLUSIONS: Although these data show the potential pleiotropic influence of CD36 SNP rs1984112 on lipoprotein accumulation in a young healthy cohort, further assessment in a larger cohort is warranted.

A candidate gene approach for identifying differential iron responses in young overweight women to an energy-restricted haem iron-rich diet.

Although iron deficiency is common in women especially during dieting, weight management trials rarely examine the longitudinal impact of genetics on iron. This study examined the associations between the TMPRSS6 rs855791 polymorphism and iron indices at baseline and after a 12-month trial comparing two weight loss diets (higher-protein, higher-haem iron (HPHI) vs lower-protein, lower-haem iron (LPLI)). A total of 76 young overweight women (18-25y; BMI⩾27.5 kg/m(2)) were included at baseline, with 27 (HPHI: n=15; LPLI: n=12) completing the 12-month trial. At baseline, C allele homozygotes exhibited higher serum iron (P=0.047) and lower hepcidin (P=0.023) compared with T allele carriers. After 12 months, no genotypic differences were observed for ferritin and soluble transferrin receptor, although C homozygotes on HPHI showed higher serum iron and transferrin saturation (P<0.05). Results indicate that rs855791 can influence iron metabolism to some extent, but its impact on storage and functional iron status is small relative to dietary protein/iron manipulation.

The major plant-derived cannabinoid Δ(9)-tetrahydrocannabinol promotes hypertrophy and macrophage infiltration in adipose tissue.

Synthetic cannabinoid receptor agonists activate lipoprotein lipase and the formation of lipid droplets in cultured adipocytes. Here we extend this work by examining whether Δ(9)-tetrahydrocannabinol (THC), a major plant-derived cannabinoid, increases adipocyte size in vivo. Further, possibly as a consequence of hypertrophy, we hypothesize that THC exposure promotes macrophage infiltration into adipose tissue, an inflammatory state observed in obese individuals. Rats repeatedly exposed to THC in vivo had reduced body weight, fat pad weight, and ingested less food over the drug injection period. However, THC promoted adipocyte hypertrophy that was accompanied by a significant increase in cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C) expression, an enzyme important in packaging triglycerides. We also showed that THC induced macrophage infiltration and increased expression of the inflammatory cytokine tumor necrosis factor alpha (TNF-α) in adipose tissue but did not induce apoptosis as measured by TUNEL staining. That THC increased adipocyte cell size in the absence of greater food intake, body weight and fat provides a unique model to explore mechanisms underlying changes in adipocyte size associated with a mild inflammatory state in fat tissue.

Leptin secretion is related to glucose-derived lipogenesis in isolated adipocytes.

OBJECTIVE: Leptin secretion in rats is regulated acutely by nutritional state. Insulin plays an important role in this acute nutritional regulation both directly and indirectly through effects on glucose metabolism. The aim of this study was to investigate if the fasting-induced suppression of leptin secretion was reversed by incubation under conditions mimicking nutritional repletion. DESIGN: Leptin secretion and glucose metabolism were measured following incubation with glucose and insulin in adipocytes isolated from fed and fasted rats. RESULTS: Leptin secretion was stimulated by incubation with glucose and insulin in adipocytes isolated from fed but not from fasted rats as was glucose flux through oxidative and lipogenic pathways. Ob expression and intracellular leptin content were decreased in adipocytes isolated from fasted rats throughout the whole incubation period. Suppression of glucose metabolism with cytochalasin B was accompanied by suppression of leptin secretion. The amount of leptin secretion correlated with the glucose incorporated into lipid under insulin-stimulated conditions. CONCLUSIONS: It is proposed that glucose incorporation into lipid, at least during insulin-stimulated conditions, reflects the metabolic status of the adipocyte and may be a more important regulator of leptin production and secretion than circulating glucose or insulin levels.

Insulin determines leptin responses during a glucose challenge in fed and fasted rats.

OBJECTIVE: Leptin secretion has been shown to respond acutely to changes in blood glucose and insulin. Nutritional state also has a marked effect on both the level of circulating leptin protein and leptin gene expression. The aim of this study was to assess whether the prior nutritional state altered the leptin secretory response to an acute glucose challenge, and to determine potential mechanisms. DESIGN: Male fed or fasted rats (200-250 g) were administered a single intravenous glucose bolus (1, 4 or 7 g/kg). The serum leptin, glucose, insulin and free fatty acid responses were studied over the following 5 h. The level of leptin gene expression and leptin protein was then determined in the epididymal fat pads, and in fed and fasted untreated rats for basal comparison. RESULTS: Leptin secretion in response to glucose was suppressed in fasted rats following all glucose doses. The total leptin response was correlated with the total insulin response in all conditions (r = 0.85) and with the glucose response in fed rats (r = 0.69). Both leptin gene expression and leptin protein content were lower in basal fasted rats. Leptin gene expression and leptin protein content still remained lower 5 h following a glucose bolus but there was partial reversal of the effects of fasting following the 7 g/kg glucose dose. CONCLUSIONS: Leptin secretion in response to an intravenous glucose bolus was determined by the insulin response and was significantly suppressed in fasted compared to fed rats. In addition to differences in the total insulin response of the animals, lower leptin responses may be facilitated by lower levels of both leptin gene mRNA and pre-existing leptin protein in epididymal adipose tissue of fasted rats.