Unanticipated Enhancement of Intestinal TG Output by Apoc3 ASO Inhibition.

BACKGROUND: The objective of this study was to investigate whether apoC3 (apolipoprotein C3) inhibition with an antisense oligonucleotide (ASO) modulates intestinal triglyceride secretion. METHODS: Sprague-Dawley rats were treated with subcutaneous injections of apoC3 ASO 25 mg/kg twice weekly or inactive ASO for 4 weeks before the assessment of lymph flow, triglyceride and apoB48 (apolipoprotein B48) appearance in the lymph. Rats were surgically implanted with catheters in the mesenteric lymph duct and duodenum. Following an overnight fast, an intraduodenal lipid bolus (1.5-mL intralipid) was administered. Lymph fluid was collected for the following 4 hours to compare effects on lymph flow, lymph triglyceride and apoB48 concentration, and secretion. To assess suppression of apoC3 expression and protein abundance by apoC3 ASO compared with inactive ASO (placebo), intestinal and hepatic tissues were collected from a subset of animals before (fasting) and after an enteral lipid bolus (post-lipid). RESULTS: ApoC3 ASO significantly reduced apoC3 mRNA expression in the liver compared with inactive ASO (fasting: 42%, P=0.0048; post-lipid: 66%, P<0.001) and in the duodenum (fasting: 29%, P=0.0424; post-lipid: 53%, P=0.0120). As expected, plasma triglyceride also decreased significantly (fasting: 74%, P<0.001; post-lipid: 33%, P=0.0276). Lymph flow and cumulative lymph volume remained unchanged following apoC3 ASO therapy; however, lymph triglyceride, but not apoB48 output, increased by 38% (ANOVA, P<0.001). Last, no changes were observed in stool triglyceride, intestinal fat (quantified via oil red O staining), and expression of mRNAs involved in triglyceride synthesis, lipid droplet formation, and chylomicron transport and secretion. CONCLUSIONS: Despite the marked reduction in plasma triglyceride concentration that occurs with apoC3 ASO inhibition, intestinal triglyceride output surprisingly increased rather than decreased. These data demonstrate that the reduction of intestinal triglyceride output does not contribute to the potent plasma triglyceride-lowering observed with this novel therapy for hypertriglyceridemia. Further studies are required to explore the mechanism of this intestinal effect.

Expanding Pharmacists' Role in the Management of Non-Alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD) stands as an increasingly pressing global health challenge, underscoring the need for timely identification to facilitate effective treatment and prevent the progression of chronic liver disorders. Given the projected scarcity of specialized healthcare professionals, particularly hepatologists and gastroenterologists, the role of pharmacists emerges as pivotal in NAFLD management. This article sheds light on the potential of pharmacists within community pharmacy settings, not as diagnostic entities, but as facilitators in recognizing and screening individuals at elevated NAFLD risk using validated non-invasive tools like portable devices and calculators. By prioritizing patient education, referrals, and continuous monitoring, pharmacists can refine NAFLD management, ultimately advancing patient outcomes. Enhancing pharmacists' impact in early NAFLD detection and management can be facilitated through collaborations with healthcare institutions and the incorporation of patient self-assessment tools. This collaborative approach holds promise for further promoting improved liver health within the community.

Glucagon-like Peptide-2 Acutely Enhances Chylomicron Secretion in Humans Without Mobilizing Cytoplasmic Lipid Droplets.

CONTEXT: A portion of ingested fats are retained in the intestine for many hours before they are mobilized and secreted in chylomicron (CM) particles. Factors such as glucagon-like peptide-2 (GLP-2) and glucose can mobilize these stored intestinal lipids and enhance CM secretion. We have recently demonstrated in rodents that GLP-2 acutely enhances CM secretion by mechanisms that do not involve the canonical CM synthetic assembly and secretory pathways. OBJECTIVE: To further investigate the mechanism of GLP-2's potent intestinal lipid mobilizing effect, we examined intracellular cytoplasmic lipid droplets (CLDs) in intestinal biopsies of humans administered GLP-2 or placebo. DESIGN, SETTING, PATIENTS, AND INTERVENTIONS: A single dose of placebo or GLP-2 was administered subcutaneously 5 hours after ingesting a high-fat bolus. In 1 subset of participants, plasma samples were collected to quantify lipid and lipoprotein concentrations for 3 hours after placebo or GLP-2. In another subset, a duodenal biopsy was obtained 1-hour after placebo or GLP-2 administration for transmission electron microscopy and proteomic analysis. RESULTS: GLP-2 significantly increased plasma triglycerides by 46% (P = 0.009), mainly in CM-sized particles by 133% (P = 0.003), without reducing duodenal CLD size or number. Several proteins of interest were identified that require further investigation to elucidate their potential role in GLP-2-mediated CM secretion. CONCLUSIONS: Unlike glucose that mobilizes enterocyte CLDs and enhances CM secretion, GLP-2 acutely increased plasma CMs without significant mobilization of CLDs, supporting our previous findings that GLP-2 does not act directly on enterocytes to enhance CM secretion and most likely mobilizes secreted CMs in the lamina propria and lymphatics.

Lipid Metabolism in Metabolic-Associated Steatotic Liver Disease (MASLD).

Metabolic-associated steatotic liver disease (MASLD) is a cluster of pathological conditions primarily developed due to the accumulation of ectopic fat in the hepatocytes. During the severe form of the disease, i.e., metabolic-associated steatohepatitis (MASH), accumulated lipids promote lipotoxicity, resulting in cellular inflammation, oxidative stress, and hepatocellular ballooning. If left untreated, the advanced form of the disease progresses to fibrosis of the tissue, resulting in irreversible hepatic cirrhosis or the development of hepatocellular carcinoma. Although numerous mechanisms have been identified as significant contributors to the development and advancement of MASLD, altered lipid metabolism continues to stand out as a major factor contributing to the disease. This paper briefly discusses the dysregulation in lipid metabolism during various stages of MASLD.

Enteral glucose, absorbed and metabolized, potently enhances mesenteric lymph flow in chow- and high-fat-fed rats.

A portion of absorbed dietary triglycerides (TG) is retained in the intestine after the postprandial period, within intracellular and extracellular compartments. This pool of TG can be mobilized in response to several stimuli, including oral glucose. The objective of this study was to determine whether oral glucose must be absorbed and metabolized to mobilize TG in rats and whether high-fat feeding, a model of insulin resistance, alters the lipid mobilization response to glucose. Lymph flow, TG concentration, TG output, and apolipoprotein B48 (apoB48) concentration and output were assessed after an intraduodenal lipid bolus in rats exposed to the following intraduodenal administrations 5 h later: saline (placebo), glucose, 2-deoxyglucose (2-DG, absorbed but not metabolized), or glucose + phlorizin (intestinal glucose absorption inhibitor). Glucose alone, but not 2-DG or glucose + phlorizin treatments, stimulated lymph flow, TG output, and apoB48 output compared with placebo. The effects of glucose in high-fat-fed rats were similar to those in chow-fed rats. In conclusion, glucose must be both absorbed and metabolized to enhance lymph flow and intestinal lipid mobilization. This effect is qualitatively and quantitatively similar in high-fat- and chow-fed rats. The precise signaling mechanism whereby enteral glucose enhances lymph flow and mobilizes enteral lipid remains to be determined.NEW & NOTEWORTHY Glucose potently enhances mesenteric lymph flow in chow- and high-fat-fed rats. The magnitude of glucose effect on lymph flow is no different in chow- and high-fat-fed rats. Glucose must be absorbed and metabolized to enhance lymph flow and mobilize intestinal lipid.

Acute Resistance Training May Have Lasting Benefit to Middle-Aged Adults.

Age-related declines in physical function can be mitigated with resistance training (RT), but most adults do not regularly exercise. We aimed to identify the magnitude and duration of benefits after RT in the Stay Strong, Stay Healthy (SSSH) program. A total of 27 adults (Repeaters n = 15; Summer Only n = 12), aged 60.7 ± 4.8 years, completed the same 8 weeks of SSSH in the summer and Repeaters continued in fall and spring months. Independent and paired t-tests and repeated-measures ANOVAs were used to test changes in survey responses and physical performance over 10 months. Both groups were similar at baseline (p > .07) and improved from pre- to post-summer for health surveys scores, 30 second-sit-to-stand, timed-up-and-go, and sit-n-reach (p ≤ .02). Additionally, Repeaters (measured data) and Summer Only (2.3% modeled decline) maintained those improvements 10 months later. Participation in 8 weeks of SSSH significantly improved physical strength and function and these improvements may last up to a year.

Role of Nutrition Education in Pharmacy Curriculum-Students' Perspectives and Attitudes.

Many pharmacists report they lack nutritional knowledge and believe the best time to educate pharmacists about nutrition is during pharmacy school. PURPOSE: This study was conducted to determine if today's pharmacy students receive education in nutrition and if they realize the importance of a nutrition course. METHODS: Ninety-five pharmacy students attending pharmacy school were surveyed in two pharmacy schools in the United States. RESULTS: The survey showed only 13.7% received nutrition education and 82.9% of students believed nutrition education should be incorporated into the pharmacy degree curriculum. When the pharmacy-related experience was taken into account, 73.3% of students believed that a nutrition course should be incorporated into the curriculum. CONCLUSION: This study suggests that pharmacy students from two major universities in Alabama and Illinois realize the importance of nutrition education and believe a nutrition course should be incorporated into the pharmacy degree curriculum.

Benefits of Resistance Training in Older Adults.

Aging is a natural process that may lead to detrimental health depending on someone's lifestyle, family history, psychological/psychosocial health, chronic medical conditions, and genetics. However, whether the later conditions lead to faster aging or vice versa, maintaining a healthy lifestyle and psychological health has been shown to delay the process of aging and its associated problems. Two major problems that older adults face today are the inability to perform everyday tasks (defined as activities of daily living) and the increased risk of falls. Lack of muscular function (including neuromuscular function) and bone health is associated with the inability to perform the Activity of Daily Living (ADL) and increased risk of falls. This risk of falls has been associated with cardiovascular-related mortality in older adults. Research has shown that resistance exercises can maintain normal blood glucose levels, lipids, and cholesterol, and hence the management of chronic conditions like cardiovascular diseases and diabetes mellitus. Additionally, resistance exercises hinder the process of muscular (and neuromuscular) damage, improve bone health and psychological health and sleep. This mini-review will discuss the benefits of resistance exercises on reversing or at least ceasing the process of developing conditions associated with aging.

Impact of a Professional Nutrition Program on a Female Cross Country Collegiate Athlete: A Case Report.

Low caloric intake or excessive energy expenditure can lead to a negative energy balance, which, in female athletes, may result in a condition called the female athlete triad. While several guidelines identified proper nutrition as a first line of treatment, little research has been reported to show the effect of a professional nutrition program (PNP) on the female athlete triad. The purpose of this case report was to measure the short- and long-term effects of a PNP on a female athlete presenting triad characteristics. A 20-year-old female track-and-field athlete at a Division I university who was in negative energy balance and amenorrheic underwent a one-month PNP. Short- and long-term effects measured by a dual X-ray absorptiometry scan prior to and after attending a PNP showed increased total energy intake from 2188 kcals to 3187 kcals, which resulted in an increase in body fat percent (BF%) from 4.7% to 6.7%. However, by the end of four months, energy intake and BF% (5.7% and 6.0%) values were reduced, respectively. After the twelve-month follow-up, BF% was increased (10.5%), suggesting that increasing energy intake to meet energy demands, without compromising athletic training, can be an effective treatment for the female athlete triad.