This study evaluated the effect of green tea extract and metformin and its interaction on markers of oxidative stress and inflammation in overweight women with insulin resistance. After screening, 120 women were randomly allocated in 4 groups: Placebo (PC): 1g of microcrystalline cellulose/day; Green tea (GT): 1 g (558 mg polyphenols) of standardized dry extract of green tea/day and 1 g of placebo/day; Metformin (MF): 1 g of metformin/day and 1 g of placebo/day; Green Tea and Metformin (GTMF): 1 g (558 mg polyphenols) and 1 g of metformin/day. All groups were followed-up for 12 weeks with assessment of oxidative damage to lipids and proteins, specific activity of antioxidant enzymes and inflammatory cytokine serum levels. The association of green tea with metformin significantly reduced IL-6 (GTMF: –29.7((–62.6)–20.2))(p = 0.004). Green tea and metformin isolated reduced TNF-α (GT: –12.1((–18.0)–(–3.5)); MF: –24.5((–38.60)–(–4.4)) compared to placebo (PB: 13.8 (1.2–29.2))(P < 0.001). Also, isolated metformin reduced TGF-β (MF: –25.1((–64.4)–0.04)) in comparison to placebo (PB: 6.3((–1.0)–16.3))(p = 0.038). However, when combined, their effects were nullified either for TNF-α (GTMF: 6.0((–5.7)–23.9) and for TGF-β (GTMF: –1.8((–32.1)–8.5). This study showed that there is a drug-nutrient interaction between green tea and metformin that is dependent on the cytokine analyzed.

Metabolic dysfunction is an established phenomenon in people with severe mental illness (SMI), and it has a higher prevalence than in the general population. It is associated with increased morbidity and mortality, and effective recognition and management are essential to enable good psychiatric care. Despite widespread awareness of this disparity for several decades, health outcomes continue to worsen, highlighting the need for more effective preventive and treatment measures. This article outlines the risk factors that contribute to metabolic dysfunction in this population, including genetic, environmental and pharmacological factors, and considers underlying metabolic pathophysiological processes as part of SMI itself. To aid discussions with patients, recognition and interpretation of metabolic risk factors are outlined, together with mitigating strategies. Novel areas of uncertainty are discussed, including the use of a ketogenic diet. This article advocates use of the term ‘metabolic psychiatry’, to increase awareness of the significant overlap between psychiatric illness and metabolic dysfunction.

Plasma levels of branched-chain amino acids (BCAA) and their metabolites, branched-chain ketoacids (BCKA), are increased in insulin resistance. We previously showed that ketoisocaproic acid (KIC) suppressed insulin-stimulated glucose transport in L6 myotubes, especially in myotubes depleted of branched-chain ketoacid dehydrogenase (BCKD), the enzyme that decarboxylates BCKA. This suggests that upregulating BCKD activity might improve insulin sensitivity. We hypothesised that increasing BCAA catabolism would upregulate insulin-stimulated glucose transport and attenuate insulin resistance induced by BCKA. L6 myotubes were either depleted of BCKD kinase (BDK), the enzyme that inhibits BCKD activity, or treated with BT2, a BDK inhibitor. Myotubes were then treated with KIC (200 μM), leucine (150 μM), BCKA (200 μM), or BCAA (400 μM) and then treated with or without insulin (100 nM). BDK depletion/inhibition rescued the suppression of insulin-stimulated glucose transport by KIC/BCKA. This was consistent with the attenuation of IRS-1 (Ser612) and S6K1 (Thr389) phosphorylation but there was no effect on Akt (Ser473) phosphorylation. The effect of leucine or BCAA on these measures was not as pronounced and BT2 did not influence the effect. Induction of the mTORC1/IRS-1 (Ser612) axis abolished the attenuating effect of BT2 treatment on glucose transport in cells treated with KIC. Surprisingly, rapamycin co-treatment with BT2 and KIC further reduced glucose transport. Our data suggests that the suppression of insulin-stimulated glucose transport by KIC/BCKA in muscle is mediated by mTORC1/S6K1 signalling. This was attenuated by upregulating BCAA catabolic flux. Thus, interventions targeting BCAA metabolism may provide benefits against insulin resistance and its sequelae.

Metabolic and inflammatory dysfunction is prevalent in middle-aged people with major mood disorders, but less is known about young people. We investigated the trajectories of sensitive metabolic (Homeostatic Model Assessment for Insulin Resistance [HOMA2-IR]) and inflammatory markers (C-reactive protein [CRP]) in 155 young people (26.9 ± 5.6 years) accessing mental health services. We examined demographic and clinical correlates, longitudinal trajectories and relationships with specific illness subtypes. Additionally, we compared the HOMA2-IR with fasting blood glucose (FBG) for sensitivity. We observed a significant increase in HOMA2-IR and CRP over time with higher baseline levels predicting greater increases, although the rate of increase diminished in those with higher baseline levels. Body mass index predicted increases in HOMA2-IR (p < 0.001), but not CRP (p = 0.135). Multinomial logistic regression revealed that higher HOMA2-IR levels were associated with 2.3-fold increased odds of the “circadian-bipolar spectrum” subtype (p = 0.033), while higher CRP levels were associated with a reduced risk of the “neurodevelopmental psychosis” subtype (p = 0.033). Standard FBG measures were insensitive in detecting early metabolic dysregulation in young people with depression. The study supports the use of more sensitive markers of metabolic dysfunction to address the longitudinal relationships between immune-metabolic dysregulation and mood disorders in young people.

Type 2 diabetes mellitus (T2DM) is a metabolic disorder that has reached epidemic proportions worldwide, posing a huge treat on people’s health and quality of life. From a pathogenetic prospective, T2DM is driven by insulin resistance defined as a blunted response of tissues to insulin which leads to chronic hyperglycaemia. Mechanistically, lipotoxicity and particularly the intracellular accumulation of ceramides in the skeletal muscle and the liver, is a primary metabolic aberration underpinning insulin resistance. Indeed, intracellular ceramide accumulation can hamper insulin signal transduction pathway thereby promoting insulin resistance. This review will provide an updated overview of the metabolic defects underlaying ceramide buildup and the molecular mechanism by which ceramides imping upon insulin signalling. Additionally, the role of specific ceramide subspecies as potential biomarkers for T2DM and the role of both long- and medium-chain saturated fatty acids as a modulator of ceramide metabolism will be discussed.

Polycystic ovary syndrome is associated with increased risks for certain metabolic disorders such as insulin resistance, non-alcoholic fatty liver disease and suppressed ovarian follicular development. This study aimed to examine whether soya isoflavones (ISF) mitigate these polycystic ovary syndrome-associated metabolic disorders in a rat model. Weanling Sprague-Dawley female rats were randomly divided into six groups and were treated with either 0 or 83 µg/d dihydrotestosterone (DHT) to induce polycystic ovary syndrome and fed diets containing 0, 0·5, or 1 g ISF/kg diet for 8 weeks. DHT treatment increased food intake, body weight gain (P < 0·001), percentage of primordial follicles (60 % v. 50·9 %, P < 0·05) and accumulation of lipid droplets in the livers. It also elevated serum total cholesterol, free cholesterol, TAG, NEFA and leptin and hepatic total cholesterol and NEFA. Additionally, DHT treatment reduced the percentage of primary follicles (13·8 % v. 30·2 %, P < 0·05), ovary weight and length (P < 0·001), as well as insulin sensitivity (P < 0·01) compared with the Control. ISF intake at 1 g/kg reduced body weight gain, serum total cholesterol, free cholesterol, NEFA, leptin and hepatic TAG and DHT-induced insulin resistance (P < 0·01). ISF intake at both levels decreased DHT-induced lipid droplet accumulation in the livers and changes in the percentages of primordial and primary follicles. Dietary soya ISF alleviated DHT-induced body weight gain, insulin resistance and hepatic lipid droplet accumulation, as well as suppressed ovarian follicular development. This suggests that the consumption of soya foods or ISF supplements may be beneficial for individuals with polycystic ovary syndrome, mitigating the associated metabolic disorders such as diabetes and non-alcoholic fatty liver disease.

A healthy diet is at the forefront of measures to prevent type 2 diabetes. Certain vegetable and fish oils, such as pine nut oil (PNO), have been demonstrated to ameliorate the adverse metabolic effects of a high-fat diet. The present study investigates the involvement of the free fatty acid receptors 1 (FFAR1) and 4 (FFAR4) in the chronic activity of hydrolysed PNO (hPNO) on high-fat diet-induced obesity and insulin resistance. Male C57BL/6J wild-type, FFAR1 knockout (-/-) and FFAR4-/- mice were placed on 60 % high-fat diet for 3 months. Mice were then dosed hPNO for 24 d, during which time body composition, energy intake and expenditure, glucose tolerance and fasting plasma insulin, leptin and adiponectin were measured. hPNO improved glucose tolerance and decreased plasma insulin in the wild-type and FFAR1-/- mice, but not the FFAR4-/- mice. hPNO also decreased high-fat diet-induced body weight gain and fat mass, whilst increasing energy expenditure and plasma adiponectin. None of these effects on energy balance were statistically significant in FFAR4-/- mice, but it was not shown that they were significantly less than in wild-type mice. In conclusion, chronic hPNO supplementation reduces the metabolically detrimental effects of high-fat diet on obesity and insulin resistance in a manner that is dependent on the presence of FFAR4.

Dietary guidelines are increasingly promoting plant-based diets, limits on red meat consumption, and plant-based sources of protein for health and environmental reasons(1). It is unclear how the resulting food substitutions associate with insulin resistance, a risk factor for type 2 diabetes. Here, we modelled the replacement of red and processed meat with plant-based alternatives and the estimated effect on insulin sensitivity. We included 783 participants (55% female) from the Childhood Determinants of Adult Health (CDAH) study, a population-based cohort of Australians. In adulthood, diet was assessed at three time points using food frequency questionnaires: CDAH-1 (2004–06), CDAH-2 (2009–11), and CDAH-3 (2017–19). The median follow-up duration was 13 years. The cumulative average intake of each food group was calculated to reflect habitual consumption. Insulin sensitivity (%) was estimated from fasting glucose and insulin concentrations at CDAH-3 (aged 39–49 years) using homeostasis model assessment. Applying the partition model(2), we simulated the replacement of one food group with another by including both in the model simultaneously (e.g., red meat and legumes), along with potential confounders and energy intake. The difference between parameter estimates (i.e., regression coefficients and variances) and their covariance were used to estimate the “substitution” effect. We report the simulated percentage point change in log-transformed insulin sensitivity for a 1 serve/day lower intake of one food group with a 1 serve/day higher intake of another food group. Replacing red meat with a combination of plant-based alternatives was associated with higher insulin sensitivity (β = 0·10, 95% CI 0·04–0·16). Adjustment for waist circumference attenuated this association by 61·4%. On an individual basis, replacing red meat with legumes (β = 0·12, 95% CI 0·02–0·21), nuts and seeds (β = 0·15, 95% CI 0·06–0·23), or whole grains (β = 0·11, 95% CI 0·04–0·17) was likewise associated with higher insulin sensitivity. Point estimates were similar when replacing processed meat with plant-based alternatives, but more uncertain due to wide confidence intervals. Our modelling suggests that habitually replacing red meat, and possibly processed meat, with plant-based alternatives may associate with higher insulin sensitivity, and thus, a lower risk of type 2 diabetes. Abdominal adiposity was identified as a potentially important mediator in this relationship. In relation to insulin sensitivity, our findings support the recommendation to choose plant-based sources of protein at the expense of red meat consumption.

Non-alcoholic fatty liver disease (NAFLD), which is a prevalent hepatic condition worldwide, is expected to develop into the leading reason for end-stage fatty liver in the forthcoming decades. Incorporating rapeseed oil into a balanced diet may be beneficial in improving NAFLD. The goal of this trial was to evaluate the impact of substituting ghee with rapeseed oil on primary outcomes such as fatty liver and liver enzymes, as well as on secondary outcomes including glycaemic variables, lipid profile and anthropometric measurements in individuals with NAFLD. Over 12 weeks, 110 patients (seventy men and forty women; BMI (mean) 28·2 (sd 1·6 kg/m2); mean age 42 (sd 9·6) years), who daily consumed ghee, were assigned to the intervention or control group through random allocation. The intervention group was advised to substitute ghee with rapeseed oil in the same amount. The control group continued the consumption of ghee and was instructed to adhere to a healthy diet. Results showed a significant reduction in the steatosis in the intervention group in comparison with the control group (P < 0·001). However, a significant change in the levels of alanine aminotransferase (–14·4 μg/l), γ-glutamyl transferase (–1·8 μg/l), TAG (–39·7 mg/dl), total cholesterol (–17·2 mg/dl), LDL (–7·5 mg/dl), fasting blood glucose (–7·5 mg/dl), insulin (–3·05 mU/l), Homeostatic Model Assessment for Insulin Resistance (–0·9), Quantitative Insulin-Sensitivity Check Index (+0·01), weight (–4·3 kg), BMI (–0·04 kg/m2), waist (–5·6 cm) and waist:height ratio (–0·04) was seen in the intervention group. The consumption of rapeseed oil instead of ghee caused improvements in liver steatosis and enzymes, glycaemic variables and anthropometric measurements among individuals with NAFLD.

Individuals with mood disorders are predisposed to metabolic dysfunction, while those with metabolic dysregulation such as diabetes and obesity experience more severe depressive symptoms. Both metabolic dysfunction and mood disorders are independently associated with cognitive deficits. Therefore, given their close association, this study aimed to explore the association between metabolic dysfunction in individuals with mood disorders in relation to cognitive outcomes. A comprehensive search comprised of these three domains was carried out; a random-effects meta-analysis pooling mean cognitive outcomes was conducted (PROSPERO ID: CRD42022295765). Sixty-three studies were included in this review; 26 were synthesized in a quantitative meta-analysis. Comorbid metabolic dysregulation was associated with significantly lower global cognition among individuals with mood disorders. These trends were significant within each mood disorder subgroup, including major depressive disorder, bipolar disorder, and self-report depression/depressive symptoms. Type 2 diabetes was associated with the lowest cognitive performance in individuals with mood disorders, followed by peripheral insulin resistance, body mass index ⩾25 kg/m2, and metabolic syndrome. Significant reduction in scores was also observed among individual cognitive domains (in descending order) of working memory, attention, executive function, processing speed, verbal memory, and visual memory. These findings demonstrate the detrimental effects of comorbid metabolic dysfunction in individuals with mood disorders. Further research is required to understand the underlying mechanisms connecting mood disorders, metabolism, and cognition.

The literature on green tea consumption and glucose metabolism has reported conflicting findings. This cross-sectional study examined the association of green tea consumption with abnormal glucose metabolism among 3000 rural residents aged 40–60 years in Khánh Hòa province in Vietnam. Multinomial logistic regression analysis was conducted to examine the association of green tea consumption (0, < 200, 200–< 400, 400–< 600 or ≥ 600 ml/d) with prediabetes and diabetes (based on the American Diabetes Association criteria). Linear regression analysis was performed to examine the association between green tea consumption and the log-transformed homeostatic model assessment of insulin resistance (HOMA-IR) (a marker of insulin resistance) and the log-transformed homeostatic model assessment of β-cell function (HOMA-β) (a marker of insulin secretion). The OR for prediabetes and diabetes among participants who consumed ≥ 600 ml/d v. those who did not consume green tea were 1·61 (95 % CI = 1·07, 2·42) and 2·04 (95 % CI = 1·07, 3·89), respectively. Higher green tea consumption was associated with a higher level of log-transformed HOMA-IR (Pfor trend = 0·04) but not with a lower level of log-transformed HOMA-β (Pfor trend = 0·75). Higher green tea consumption was positively associated with the prevalence of prediabetes, diabetes and insulin resistance in rural Vietnam. The findings of this study indicated prompting the need for further research considering context in understanding the link between green tea consumption and glucose metabolism, especially in rural settings in low- and middle-income countries.

Dietary guidelines are increasingly promoting mostly plant-based diets, limits on red meat consumption, and plant-based sources of protein for health and environmental reasons. It is unclear how the resulting food substitutions associate with insulin resistance, a risk factor for type 2 diabetes. We modelled the replacement of red and processed meat with plant-based alternatives and the estimated effect on insulin sensitivity. We included 783 participants (55 % female) from the Childhood Determinants of Adult Health study, a population-based cohort of Australians. In adulthood, diet was assessed at three time points using FFQ: 2004–2006, 2009–2011 and 2017–2019. We calculated the average daily intake of each food group in standard serves. Insulin sensitivity was estimated from fasting glucose and insulin concentrations in 2017–2019 (aged 39–49 years) using homoeostasis model assessment. Replacing red meat with a combination of plant-based alternatives was associated with higher insulin sensitivity (β = 10·5 percentage points, 95 % CI (4·1, 17·4)). Adjustment for waist circumference attenuated this association by 61·7 %. Replacing red meat with either legumes, nuts/seeds or wholegrains was likewise associated with higher insulin sensitivity. Point estimates were similar but less precise when replacing processed meat with plant-based alternatives. Our modelling suggests that regularly replacing red meat, and possibly processed meat, with plant-based alternatives may associate with higher insulin sensitivity. Further, abdominal adiposity may be an important mediator in this relationship. Our findings support advice to prioritise plant-based sources of protein at the expense of red meat consumption.

Long-chain n-3 PUFA (LC n-3 PUFA) prevent, in rodents, insulin resistance (IR) induced by a high-fat and/or fructose diet but not IR induced by glucocorticoids. In humans, contrasting effects have also been reported. We investigated their effects on insulin sensitivity, feed intake (FI) and body weight gain in genetically insulin resistant male obese (fa/fa) Zucker (ZO) rats during the development of obesity. ZO rats were fed a diet supplemented with 7 % fish oil (FO) + 1 % corn oil (CO) (wt/wt) (ZOFO), while the control group was fed a diet containing 8 % fat from CO (wt/wt) (ZOCO). Male lean Zucker (ZL) rats fed either FO (ZLFO) or CO (ZLCO) diet were used as controls. FO was a marine-derived TAG oil containing EPA 90 mg/g + DHA 430 mg/g. During an oral glucose tolerance test, glucose tolerance remained unaltered by FO while insulin response was reduced in ZOFO only. Liver insulin sensitivity (euglycaemic–hyperinsulinaemic clamp + 2 deoxyglucose) was improved in ZOFO rats, linked to changes in phosphoenolpyruvate carboxykinase expression, activity and glucose-6-phosphatase activity. FI in response to intra-carotid insulin/glucose infusion was decreased similarly in ZOFO and ZOCO. Hypothalamic ceramides levels were lower in ZOFO than in ZOCO. Our study demonstrates that LC n-3 PUFA can minimise weight gain, possibly by alleviating hypothalamic lipotoxicity, and liver IR in genetically obese Zucker rats.

We sought to examine the effects of daily consumption of macadamia nuts on body weight and composition, plasma lipids and glycaemic parameters in a free-living environment in overweight and obese adults at elevated cardiometabolic risk. Utilising a randomised cross-over design, thirty-five adults with abdominal obesity consumed their usual diet plus macadamia nuts (~15 % of daily calories) for 8 weeks (intervention) and their usual diet without nuts for 8 weeks (control), with a 2-week washout. Body composition was determined by bioelectrical impedance; dietary intake was assessed with 24-h dietary recalls. Consumption of macadamia nuts led to increased total fat and MUFA intake while SFA intake was unaltered. With mixed model regression analysis, no significant changes in mean weight, BMI, waist circumference, percent body fat or glycaemic parameters, and non-significant reductions in plasma total cholesterol of 2⋅1 % (−4⋅3 mg/dl; 95 % CI −14⋅8, 6⋅1) and low-density lipoprotein (LDL-C) of 4 % (−4⋅7 mg/dl; 95 % CI −14⋅3, 4⋅8) were observed. Cholesterol-lowering effects were modified by adiposity: greater lipid lowering occurred in those with overweight v. obesity, and in those with less than the median percent body fat. Daily consumption of macadamia nuts does not lead to gains in weight or body fat under free-living conditions in overweight or obese adults; non-significant cholesterol lowering occurred without altering saturated fat intake of similar magnitude to cholesterol lowering seen with other nuts.

Clinical Trial Registry Number and Website: NCT03801837 https://clinicaltrials.gov/ct2/show/NCT03801837?term = macadamia + nut&draw = 2&rank = 1

The precision nutrition paradigm is based on the premise that substantial variation exists between human subjects in terms of diet-related disease risk and response to dietary interventions. In terms of better defining, ‘the right diet for the right person at the right time’ may be more appropriate than ‘one-diet-fits-all’. This review will explore how systems biology and nutrigenomics approaches have advanced the precision nutrition paradigm. We will draw upon a number of elegant mechanistic studies that have enhanced our understanding with respect to the complex biology and inter-organ crosstalk, relating to inflammation and metabolism, that underpin cardio-metabolic health. Also, this review will explore the extent to which more targeted, precision nutrition approaches may attenuate adverse risk factors associated with cardio-metabolic disease. We will focus on the key characteristics or ‘metabotypes’ of high- v. low-risk individuals and response v. non-response to interventions, to generate greater insights with respect to risk stratification and therapeutic interventions to enhance disease prevention. The goal is to utilise systems biology to enhance understanding by underpinning more targeted nutritional approaches, which may improve efficacy of personalised nutrition interventions.

The study aimed to explore the relationships of skeletal muscle mass with disease severity in metabolic-associated fatty liver disease (MAFLD) patients with different methods. Consecutive subjects undergoing bioelectrical impedance analysis were included. The steatosis grade and liver fibrosis were evaluated by MRI-derived proton density fat fraction and two-dimensional shear wave elastography. The appendicular skeletal muscle mass (ASM) was adjusted by height2 (ASM/H2), weight (ASM/W) and BMI (ASM/BMI). Overall, 2223 subjects (50·5 %, MAFLD; 46·9 %, male) were included, with the mean age 37·4 ± 10·6 years. In multivariate logistic regression analysis, the subjects with the lowest quartile (Q1) of ASM/W or ASM/BMI had higher risk ratios for MAFLD (OR (95 % CI) in male: 2·57 (1·35, 4·89), 2·11(1·22, 3·64); in female: 4·85 (2·33, 10·01), 4·81 (2·52, 9·16), all P < 0·05, all for Q1 v. Q4). The MAFLD patients with lower quartiles of ASM/W had the higher risk OR for insulin resistance (IR), both in male and female (2·14 (1·16, 3·97), 4·26 (1·29, 14·02) for Q4 v. Q1, both P < 0·05). While the significant OR were not observed when ASM/H2 and ASM/BMI were used. There were significant dose-dependent associations between decreased ASM/W as well as ASM/BMI and moderate–severe steatosis (2·85(1·54, 5·29), 1·90(1·09, 3·31), both P < 0·05) in male MAFLD patients. In conclusion, ASM/W is superior to ASM/H2 and ASM/BMI in predicting the degree of MAFLD. A lower ASM/W is associated with IR and moderate–severe steatosis in non-elderly male MAFLD.

An abnormal Zn status has been suggested to play a role in the pathogenesis of type 2 diabetes. However, epidemiological studies of the relationship between plasma Zn concentrations and diabetes are sparse and inconclusive. We aimed to investigate the association between plasma Zn concentrations and glycaemic markers (fasting glucose, 2-h glucose and homeostatic model assessment of insulin resistance) in rural and urban Cameroon. We studied 596 healthy adults (63·3 % women) aged 25–55 years in a population-based cross-sectional study. The mean plasma Zn concentration was 13·7 ± 2·7 µmol/L overall, with higher levels in men (14·4 ± 2·9 µmol/l) than in women (13·2 ± 2·6 µmol/l), P-value < 0·0001. There was an inverse relationship between tertiles of plasma Zn and 2-h glucose concentrations (P-value for linear trend = 0·002). The difference in 2-h glucose between those in the highest tertile of plasma Zn compared to the lowest was −0·63 (95 % CI − 1·02, −0·23) mmol/l. This remained significant after adjusting for age, sex, smoking status, alcohol intake, education level, area of residence, adiposity and objectively measured physical activity −0·43(–0·82, −0·04). Similar inverse associations were observed between plasma Zn concentrations and fasting glucose and homeostatic model assessment of insulin resistance when adjusted for socio-demographic and health-related behavioural characteristics. The current findings of an inverse association between plasma Zn concentrations and several markers of glucose homeostasis, together with growing evidence from intervention studies, suggest a role for Zn in glucose metabolism. If supported by further evidence, strategies to improve Zn status in populations may provide a cheap public health prevention approach for diabetes.

This study investigated whether long-chain n-3 PUFA (LC n-3 PUFA) given to pregnant rats fed a high-fat (HF) diet may prevent fetal programming in male offspring at adulthood. Six weeks before mating, and throughout gestation and lactation, female nulliparous Sprague–Dawley rats were given a chow (C) diet, HF (60·6 % fat from maize, rapeseed oils and lard) or HF in which one-third of fat was replaced by fish oil (HF n-3). At weaning, the three offspring groups were randomly separated in two groups fed C diet, or HF without LC n-3 PUFA, for 7 weeks until adulthood. Glucose tolerance and insulin sensitivity were assessed by an oral glucose tolerance test both at weaning and at adulthood. Insulin signalling was determined in liver, muscle and adipose tissue by quantification of the phosphorylation of Akt on Ser 473 at adulthood. At weaning, as at adulthood, offspring from HF-fed dams were obese and displayed glucose intolerance (GI) and insulin resistance (IR), but not those from HFn-3 fed dams. Following the post-weaning C diet, phosphorylation of Akt was strongly reduced in all tissues of offspring from HF dams, but to a lesser extent in liver and muscle of offspring from HFn-3 dams. However, it was abolished in all tissues of all offspring groups fed the HF post-weaning diet. Thus, LC n-3 PUFA introduced in a HF in dams partially prevented the transmission of GI and IR in adult offspring even though they were fed without LC n-3 PUFA from weaning.