A positive association has been demonstrated between consumption of sucrose-sweetened beverages and the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD). Since the administration of 30 % sucrose in the drinking water (sucrose-rich diet (SRD)) to rats has proven to be a good model of systemic insulin resistance, the aim of our study was to analyse the effect of caloric restriction applied on SRD-treated rats by switching back to a standard diet, on liver morphology, function and metabolism. Consumption of an SRD causes a metabolic shift towards gluconeogenesis and fatty acid synthesis leading to an increase in TAG levels in plasma and in the liver that were associated with a decrease in insulin sensitivity. Moreover, our results show that animals fed an SRD develop steatohepatitis characterised by the generation of oxidative stress, endoplasmic reticulum (ER) stress, inflammation and apoptosis. Although no histological changes were observed after a 2-week caloric restriction, key pathways associated with the progression of MASLD as inflammation, ER stress and apoptosis were slowed down. Notably, this 2-week intervention also increased liver insulin sensitivity (evaluated by AKT activity in this tissue) and drove the lipid metabolic profile towards oxidation, thus lowering circulating TAG levels. In summary, the present study uncovers underlying mechanisms affected, and their metabolic consequences, during the first stages of the phenotypic reversal of steatohepatitis by switching back to a standard diet after receiving sucrose-sweetened water for several weeks.

Lipids play an important role in human nutrition. Although adequate lipid consumption is necessary for an optimal functioning of the human body, overconsumption of saturated fatty acids can lead to postprandial hypertriglyceridaemia, which triggers the development of atherosclerosis. Important parameters that impact postprandial lipaemia and inflammation are related to the matrix structure and the fat-soluble micronutrient profile of ingested foods/lipids, but the specific effect of these parameters should be further studied, as most of the available studies evaluate their effect at fasting state. This review specifically explores the effects of food structure and fat-soluble micronutrients, from either micronutrient-rich foods or supplements, on postprandial hypertriglyceridaemia and inflammation. The review also highlights the potential of emerging biomarkers such as miRNAs or circulating microvesicles, as an alternative to the widely use biomarkers (e.g. low-density lipoproteins or blood concentration of pro-inflammatory cytokines), to identify inflammation associated with postprandial hypertriglyceridaemia at early stages.

A high dose of whey protein hydrolysate fed with milk minerals rich in calcium (Capolac®) results in enhanced glucagon-like peptide-1 (GLP-1) concentrations in lean individuals; however, the effect of different calcium doses ingested alongside protein is unknown. The present study assessed the dose response of calcium fed alongside 25 g whey protein hydrolysate on GLP-1 concentrations in individuals with overweight/obesity. Eighteen adults (mean ± sd: 8M/10F, 34 ± 18 years, 28·2 ± 2·9 kgm−2) completed four trials in a randomised, double-blind, crossover design. Participants consumed test solutions consisting of 25 g whey protein hydrolysate (CON), supplemented with 3179 mg (LOW), 6363 mg (MED) or 9547 mg (HIGH) Capolac® on different occasions, separated by at least 48 h. The calcium content of test solutions equated to 65, 892, 1719 and 2547 mg, respectively. Arterialised-venous blood was sampled over 180 min to determine plasma concentrations of GLP-1TOTAL, GLP-17–36amide, insulin, glucose, NEFA, and serum concentrations of calcium and albumin. Ad libitum energy intake was measured at 180 min. Time–averaged incremental AUC (iAUC) for GLP-1TOTAL (pmol·l−1·min−1) did not differ between CON (23 ± 4), LOW (25 ± 6), MED (24 ± 5) and HIGH (24 ± 6). Energy intake (kcal) did not differ between CON (940 ± 387), LOW (884 ± 345), MED (920 ± 334) and HIGH (973 ± 390). Co-ingestion of whey protein hydrolysate with Capolac® does not potentiate GLP-1 release in comparison with whey protein hydrolysate alone. The study was registered at clinical trials (NCT03819972).

A divergent selection experiment on litter size variability (high and low lines) was performed in rabbits over seven generations. The aim of this study was to evaluate the correlated responses to selection in body condition and fat reserves mobilisation. Litter size variability was estimated as phenotypic variance of litter size within female after correcting for the year-season and the parity-lactation status effects. A total of 226 females were used in this study, of which 158 females were used to measure body condition and energy mobilisation. Body condition was measured as BW and perirenal fat thickness. Females were stimulated with the adrenergic isoproterenol. Mobilisation capacity of fat reserves was measured by the lipolytic potential, defined as the increment in non-esterified fatty acids (NEFA) levels from basal concentration until adrenergic stimulation at mating, delivery and 10 days after delivery of the second reproductive cycle. Females were classified as survivor or non-survivor when they were culled for sanitary reasons or died before the third kindling. Data were analysed using Bayesian methodology. Survivor females presented higher BW than the non-survivor females at delivery (238 g, P=1.00) and 10 days after delivery (276 g, P=1.00). They also showed higher perirenal fat thickness at 10 days after delivery (0.62 mm, P=1.00). At delivery, basal NEFA levels was lower in survivor than non-survivor females (−0.18 mmol/l, P=1.00), but their lipolytic potential (∆NEFA) was higher (0.08 mmol/l, P=0.94). Body weight was similar between lines in survivor females. Perirenal fat thickness was lower in the high line than in the low line at delivery (−0.23 mm, P=0.90) and 10 days after delivery (−0.28 mm, P=0.92). The high line exhibited higher NEFA (0.10 mmol/l, P=0.93) and lower ∆NEFA (−0.08 mmol/l, P=0.92) than the low line at delivery. The low line showed a favourable correlated response to selection on body condition and fat reserves mobilisation. In conclusion, the low line selected for litter size variability seems to adapt better to adverse conditions, as it has a greater capacity to mobilise energy reserves at delivery than the high line. Females that adequately manage their body reserves and perform energy mobilisation correctly have a lower risk of dying or being culled.

The purpose of the present study was to determine the effects of an exercise training programme in high-fat-fed rats on in vitro lipolysis in a visceral (mesenteric) and a non-visceral fat depot (retroperitoneal) and its relationship to perilipin content. Two groups of female rats were fed a high-fat diet (42 % as energy) for 8 weeks, one remaining sedentary (Sed) and the other being exercise trained (Tr) for this entire period. Rats were killed after 2 and 8 weeks of their respective treatment. The significantly (P < 0·01) higher levels in mesenteric and retroperitoneal fat pad weights, plasma leptin, NEFA and glucose observed with time in Sed high-fat-fed rats were significantly (P < 0·05) attenuated in Tr animals. Isoproterenol-stimulated (10− 5–10− 4 m) lipolysis in the mesenteric, but not in the retroperitoneal tissue, was significantly (P < 0·05) lower (about 57 %) in Tr than in Sed rats after 8 weeks of high-fat feeding. The isoproterenol-stimulated lipolysis in the mesenteric tissue of 8-week Tr high-fat-fed rats was lowered to the level measured in 2-week fat-fed rats although mesenteric fat accumulation was still significantly (P < 0·01) higher in 8- than in 2-week Tr rats. Perilipin content (Western blot) was not affected by the exercise training programme. These results indicate that exercise training resulted in a reduction in the high-fat diet-induced elevated levels of lipolysis in the mesenteric tissue. This response appears to be independent of the perilipin content.

Maternal adipose tissue is a major contributor to breast milk long-chain fatty acids, probably through the pool of plasma NEFA. The fatty acid composition of the erythrocyte membrane (EM) is a biochemical index of the intake of fatty acids not synthesized endogenously and of PUFA and long-chain PUFA fatty acid status. The present study investigated the associations between breast milk fatty acid composition and the composition of plasma NEFA and of EM fatty acids with special reference to PUFA, long-chain PUFA and conjugated linoleic acid (CLA). The detailed fatty acid composition of mature breast milk was also reported. Thirty-three healthy, lactating Brazilian women donated milk samples; of these, twenty-four also donated blood samples in an observational cross-sectional study. Breast milk fatty acid composition presented several associations with NEFA and EM composition, which explained most (≥50%) of the variability of selected milk PUFA, long-chain PUFA and CLA. Milk CLA was associated with fatty acids that are markers of dairy fat intake in the diet, NEFA and EM. In general, breast milk n-3 fatty acids and CLA, but not n-6 fatty acids, were associated with EM composition, whereas both the n-6 and n-3 fatty acids and CLA in milk were associated with NEFA composition, possibly owing to its role as a direct source of fatty acids for breast milk. These findings emphasize the contribution of the NEFA pool derived from the adipose tissue to the long-chain fatty acid composition of breast milk.

To assess the effects of acute dietary saturated fat intake on glucose-induced insulin secretion rate (ISR), measured by the C-peptide deconvolution method, and on insulin clearance and sensitivity, five obese and five normal-weight women (controls) were studied after either a 100g oral butter load or a 100ml water load. At 120min after the oral load a hyperglycaemic clamp was performed over 180min. A dramatic increase of ISR occurred after butter compared with the water challenge in the controls (1305·6 (SE 124·1) v. 616·1 (SE 52·5) pmol/min; P<0·01) and to a lesser degree in the obese subjects (1975·0 (SE 44·1) v. 1417·5 (SE 56·0) pmol/min; P<0·05). Insulin sensitivity was impaired after butter (0·60×10−2 (SE 0·11×10−2) v. 2·26×10−2 (SE 0·32×10−2) ml/min per kgFFM per (pmol/l); P<0·01) in the controls but not in the obese group. Insulin clearance during the clamp was reduced after butter compared with after the water load only in the controls (0·89 (SE 0·22) v. 1·70 (SE 0·15) litres/min; P<0·01). The data are consistent with the hypothesis that acute excess lipid availability may lead to a compensatory elevation in glucose-induced insulin secretion as a result of the decline in insulin sensitivity and a reduced insulin clearance.

It was previously shown that a high plasma concentration of non-esterified fatty acids (NEFA) persisted after a fatty breakfast, but not after an isoenergetic carbohydrate breakfast, adversely affecting glucose tolerance. The higher concentration after the fatty breakfast may in part have been a result of different mobilization rates of fatty acids. This factor can be investigated as NEFA mobilized from tissues are monounsaturated to a greater extent than those deposited from a typical meal. Twenty-four middle-aged healthy Caucasian men were given oral glucose tolerance tests (OGTT), and for 28 d isoenergetic breakfasts of similar fat composition but of low (L) or moderate (M) fat content. The composition of NEFA in fasting and postprandial plasma was determined on days 1 and 29. No significant treatment differences in fasting NEFA composition occurred on day 29. During the OGTT and 0–1 h following breakfast there was an increase in plasma long-chain saturated NEFA but a decrease in monounsaturated NEFA (μg/100 μg total NEFA; P<0·001). Between 1 and 3 h following breakfast treatment differences occurred for total saturated and total monounsaturated fatty acids (μg/100 μg total NEFA; P<0·05), expressed as an increase in 18 : 1 and decreases in 16 : 0 and 17 : 0 in treatment M relative to treatment L (P<0·05). Serum insulin attained 35 and 65 mU/l in treatments M and L respectively during this period. Negative correlations were found between 16 : 0 in fasting plasma and both waist:hip circumference (P=0·0009) and insulin response curve area during OGTT (within treatment M, P=0·0001). It is concluded that a normal postprandial insulin response is associated with a rapid change in plasma saturated:monounsaturated NEFA. It is proposed that this change is the result of a variable suppression of fat mobilization, which may partly account for a large difference in postprandial total plasma NEFA between fatty and carbohydrate meals.

Plasma triacylglycerol concentrations increase after the acute ingestion of alcohol (specifically ethanol). However, the effect of ethanol when consumed with a mixed meal has not been well studied. The objective of the present study was to determine the perturbations of lipid metabolism that occur after ingestion of ethanol in combination with a mixed meal of specific fatty acid composition. Blood samples were taken from seven healthy male subjects before and after a mixed meal, with and without ethanol. The specific fatty acid composition of the test meal allowed the fatty acids to be traced into the plasma non-esterified fatty acid pool during the postprandial period. Statistical analysis by repeated measures ANOVA showed significant effects of ethanol. For example, postprandial lipaemia was enhanced after the ethanol test meal compared with the control (P < 0·05), mainly due to increases in triacylglycerol-rich lipoproteins in the flotation range Sf 60–400 (VLDL1) (P < 0·05); those in the range Sf 20–60 (VLDL2) and also Sf > 400 (chylomicrons) were not significantly affected. The later postprandial increase in plasma non-esterified fatty acid concentrations was reduced after the ingestion of ethanol (P < 0·001), but the proportions of palmitoleic acid (a marker of fatty acid content of the test meal) and of linoleic acid (a marker of endogenous lipolysis) were not affected. The results suggest a primary effect of ethanol on the stimulation of secretion of large VLDL particles, which then compete for clearance with chylomicrons by lipoprotein lipase. The results do not support an effect of ethanol on the release of non-esterified fatty acid into the plasma. The suppression of plasma non-esterified fatty acid concentrations during the postprandial period may contribute towards the beneficial effects of moderate ethanol consumption.

The association between abdominal fat accumulation and risk of chronic diseases, including type II diabetes and coronary heart disease, has long been recognized. Insulin resistance may be a key factor in this link. Many studies have pointed to an association between insulin resistance and intra-abdominal fat accumulation (visceral obesity). However there is no clear proof of a causal link between visceral fat accumulation and insulin resistance. In assessing the probability of a causal link, it is useful to consider potential mechanisms. One such potential causal link is the release of non-esterified fatty acids from visceral fat into the portal vein, so that they have direct effects on hepatic metabolism. Visceral fat has been shown in many studies to exhibit a high rate of lipolysis compared with subcutaneous fat depots. However, if the idea that visceral fat releases fatty acids into the portal vein at a high rate is examined critically, a number of difficulties appear. Not least of these is the fact that continued high rates of lipolysis should lead to the disappearance of the visceral fat depot, unless these high rates of fat mobilization are matched by high rates of fat deposition. There is far less evidence for high rates of fat deposition in visceral adipose tissue, and some contrary evidence. Evidence for high rates of visceral lipolysis in vivo from studies involving catheterization of the portal vein is not strong. If this potential link is discounted, then other reasons for the relationship between visceral fat and insulin resistance must be considered. One is that there is no direct causal link, but both co-correlate with some other variable. A possibility is that this other variable is subcutaneous abdominal fat, which usually outweighs intra-abdominal fat several-fold. Subcutaneous fat probably plays the major role in determining systemic plasma non-esterified fatty acid concentrations, which are relevant in determining insulin resistance. In conclusion, there is at present no proof of a causal link between visceral fat accumulation and insulin resistance, or the associated metabolic syndrome. The possibility of co-correlation with some other factor, such as subcutaneous abdominal fat accumulation, must not be forgotten.

Three experiments were conducted in healthy middle-aged volunteers (six males and six females in Expt 1, six males and two females in Expt 2 and twelve males in Expt 3) with a mean BMI of 27 kg/m2 to determine whether there is a difference between morning and afternoon dietary fat clearance and utilization, and to determine in what way the fat and starch contents of the meal influence postprandial blood lipid metabolites over 4·5 h. Over 4 days in Expt 1 each subject received isoenergetic, high-carbohydrate (L, 5·5 g mixed fat/meal) and moderately high-fat (M, 33 g mixed fat/meal) breakfasts and lunches, in three combinations (LL, MM, LM), or they fasted at breakfast time and received a high fat lunch (NM) in a randomized and balanced arrangement. Each evening a standard meal was given. The following effects were significant (P<0·05): plasma triacylglycerol (TAG) responses were greater following M meals; plasma TAG concentrations were greater in the afternoon than in the morning, following two meals of the same composition, although the postprandial incremental response was less following lunch than following breakfast and peak responses were reached much earlier than after breakfast; a low-fat breakfast, or fasting at breakfast time, delayed the peak TAG response to a M lunch. The plasma concentrations of non-esterified fatty acids (NEFA) and of free glycerol were higher in the afternoon following M meals at breakfast and lunch, especially in males. This response was reduced, by the L breakfast preceding the M lunch. Two M meals in succession lowered plasma HDL-cholesterol concentration. In Expt 2 each subject received a very low-fat (VL) breakfast, followed by a lunch of the same composition. Each of these meals was followed, 110 min from the start of eating, by an infusion of Intralipid 10% emulsion at the rate of 1 ml/kg body weight over 60 s. Clearance rates of Intralipid were faster in the afternoon than in the morning (P= 0·024). In Expt 3 twelve subjects were randomly allocated to either treatment MM or LM meal patterns, as given in Expt 1. These were given daily for a period of 17 d, during which the change in fasting plasma TAG concentration was similar in both treatments. On days 1, 16 and 17 responses were measured to the M lunch and to a glucose tolerance test (GTT), conducted 2 h 17 min after lunch. The post-lunch responses confirmed those found in Expt 1; but immediately following the glucose dose there was an abrupt increase in plasma TAG that was greater in treatment LM than in treatment MM (P= 0·025), whereas plasma NEFA concentration decreased rapidly in both treatments at that time (P = 0·00066)

The β-agonist ractopamine (RAC) promotes protein deposition with little effect on fat deposition in the pig. To assess whether the lack of effect on fat deposition was due to changes in response to homeostatic signals, eight crossbred gilts (73 kg body weight (BW)) with venous catheters were used to examine plasma metabolite and hormone concentrations before and after intravenous injections of insulin and the β2-agonist fenoterol during dietary RAC (0 or 20 mg/kg) treatment. Pigs received intravenous challenges of insulin (1μg/kg BW) on days 3, 9 and 23 and fenoterol (2 μg/kg BW) on days 4, 10 and 24 of treatment. RAC was then withdrawn from the diet and insulin and fenoterol challenges were repeated 6 and 7 d later respectively. Blood samples for the determination of metabolite and hormone concentrations were taken at -30, -20, -10, -1, 2·5, 5, 10, 20, 30, 45, 60 and 120 min relative to the challenges. Dietary RAC decreased basal plasma insulin concentrations but had no effect on plasma glucose or non-esterified fatty acids (NEFA). Hypoglycaemic responses to insulin were not affected by RAC while the anti-lipolytic effects of insulin tended to be augmented. Dietary RAC decreased the lipolytic response to fenoterol, this being evident after 4 d treatment. Hypoglycaemic response to fenoterol was not changed whereas the hyperinsulinaemic response to fenterol was attenuated by dietary RAC. Previous treatment with RAC did not influence basal hormone and metabolite concentrations or responses to homeostatic signals during the withdrawal period. While these results suggest little change in glucose metabolism, the de-sensitization of adipose tissue β-adrenergic receptors is consistent with the observations that dietary RAC has little effect on the rate of fat deposition in the growing pig.

Non-esterified fatty acid (NEFA) and glycerol kinetics were studied in lactating goats to gain insight into the mechanisms by which animals in early lactation can initially mobilize and later replenish body fat reserves. Kinetic measurements were made at days 10, 38 and 76 post-partum in ten multiparous lactating does. Plasma NEFA concentrations and NEFA entry rate decreased as lactation advanced, being significantly higher at day 10 than at either days 38 or 76 of lactation. Both plasma NEFA concentrations and NEFA entry rate were negatively correlated with calculated energy balance. In contrast, glycerol entry rate was significantly higher at day 76 than at day 10 of lactation and was positively related to both calculated energy intake and energy balance. Apparent intracellular fatty acid re-esterification was lower at day 10 than at later stages of lactation and was positively related to calculated energy balance. It is suggested that during early lactation, substantial shifts in adipose tissue fat reserves can occur via altering rates of fatty acid re-esterification and de novo lipogenesis, without major changes in the rate of lipolysis.

During early lactation ruminants can mobilize considerable amounts of body fat to maintain milk production. The aim of the present study was to evaluate the efficacy of tritiated water (TOH) and non-esterified fatty acid (NEFA) kinetics as means of monitoring adipose tissue fat mobilization in lactating goats. Body fat, as estimated by a two-pool model of TOH kinetics, and NEFA entry rate were measured in four primiparous goats at days 11, 37 and 72 post partum. Estimated body fat decreased by an average of 64 g/d between days 11 and 37 of lactation, tending to increase between days 37 and 72. Plasma NEFA concentrations and NEFA entry rate decreased as lactation advanced, being significantly lower at day 72 than at day 11 of lactation. Both plasma concentrations of NEFA and NEFA entry rate were negatively correlated with calculated energy balance. Plasma NEFA concentrations and NEFA entry rate at days 11 and 37 of lactation were positively related to average body fat losses over the subsequent stage of lactation. These results demonstrate that NEFA kinetics reflect fat mobilization in primiparous lactating goats, particularly during negative energy balance.