Feeding rainbow trout with a lipid-enriched diet: effects on fatty acid sensing, regulation of food intake and cellular signaling pathways.

Using rainbow trout fed with low-fat or high-fat diets, we aimed to determine whether the response of food intake, mRNA abundance of hypothalamic neuropeptides involved in the metabolic regulation of food intake and fatty acid sensing systems in the hypothalamus and liver are similar to results previously observed when levels of specific fatty acids were raised by injection. Moreover, we also aimed to determine if the phosphorylation state of intracellular energy sensor 5'-AMP-activated protein kinase (AMPK), and proteins involved in cellular signaling such as protein kinase B (Akt) and target of rapamycin (mTOR) display changes that could be related to fatty acid sensing and the control of food intake. The increased levels of fatty acids in the hypothalamus and liver of rainbow trout fed with a high-fat diet only partially activated fatty acid sensing systems and did not elicit changes in food intake, suggesting that the fatty acid sensing response in fish is more dependent on the presence of specific fatty acids, such as oleate or octanoate, rather than to the global increase in fatty acids. We also obtained, for the first time in fish, evidence for the presence and function of energy sensors such as AMPK and proteins involved in cellular signaling, like mTOR and Akt, in the hypothalamus. These proteins in the hypothalamus and liver were generally activated in fish fed the high-fat versus low-fat diet, suggesting that cellular signaling pathways are activated in response to the increased availability of fatty acids.

A neutral lipid-enriched diet improves myelination and alleviates peripheral nerve pathology in neuropathic mice.

Charcot-Marie-Tooth (CMT) diseases comprise a genetically heterogeneous group of hereditary peripheral neuropathies. Trembler J (TrJ) mice carry a spontaneous mutation in peripheral myelin protein 22 (PMP22) and model early-onset, severe CMT type 1E disease. Recent studies indicate that phospholipid substitution, or cholesterol-enriched diet, benefit myelinated nerves, however such interventions have not been tested in early-onset dysmyelinating neuropathies. Here, we examined the lipid profile of peripheral nerves from 6-month-old TrJ mice with advanced neuropathy and tested the impact of a 6-week-long neutral lipid-enriched high-fat diet (HFD) on neuropathy progression in young, newly-weaned mice. Oil Red O staining showed pronounced neutral lipid accumulation in nerves from 6-month-old TrJ mice, along with elevated levels of key cholesterol and triglyceride transport proteins including apoE, LRP1 and ABCA1, compared with wild type (Wt). In young mice, the short-term HFD intervention increased serum cholesterol levels without impacting triglycerides, or body and liver weights. Tissue samples from neuropathic TrJ mice showed improvements in the maintenance of myelinated axons after the 6-week-long dietary intervention, and this effect was evident both in the sciatic and phrenic nerves. Concomitantly, aberrant Schwann cell proliferation was attenuated, as detected by reduction in mitotic markers and in c-Jun expression. Nerves from HFD-fed TrJ mice contained fewer macrophages, with a normalized count of CD11b + cells. In addition, we detected an increase in neutral lipids in the nerve endoneurium and a trend toward normalization of apoE, LRP1, and ABCA1 expression after the HFD feeding. Together, these results demonstrate the beneficial influence of a short-term neutral lipid-enriched diet on neuropathy progression in young TrJ mice and support further work in investigating the potential benefits of dietary lipids on hereditary neuropathies.

Magnesium-deficient high-fat diet: effects on adiposity, lipid profile and insulin sensitivity in growing rats.

BACKGROUND & AIMS: To determine if magnesium deficiency aggravates the effects of a high-fat diet in growing rats in terms of obesity, lipid profile and insulin resistance. METHODS: The study population comprised 48 newly weaned male Wistar Hannover rats distributed into four groups according to diet, namely, control group (CT; n = 8), control diet provided ad libitum; pair-feeding control group (PF; n = 16), control diet but in the same controlled amount as animals that received high-fat diets; high-fat diet group (HF; n = 12), and magnesium-deficient high-fat diet group (HFMg(-); n = 12). The parameters investigated were adiposity index, lipid profile, magnesium status, insulin sensitivity and the phosphorylation of proteins involved in the insulin-signaling pathway, i.e. insulin receptor ß-subunit, insulin receptor substrate 1 and protein kinase B. RESULTS: The HF and HFMg(-) groups were similar regarding gain in body mass, adiposity index and lipid profile, but were significantly different from the PF group. The HFMg(-) group exhibited alterations in magnesium homeostasis as revealed by the reduction in urinary and bone concentrations of the mineral. No inter-group differences were observed regarding glucose homeostasis. Protein phosphorylation in the insulin-signaling pathway was significantly reduced in the high-fat groups compared with the control groups, demonstrating that the intake of fat-rich diets increased insulin resistance, a syndrome that was aggravated by magnesium deficiency. CONCLUSIONS: Under the experimental conditions tested, the intake of a magnesium-deficient high-fat diet led to alterations in the insulin-signaling pathway and, consequently, increased insulin resistance.