We hypothesized that media long-chain fatty acids (LCFA) would more greatly depress cyclic adenosine monophosphate (cAMP), glycerol, and free fatty acid (FFA) concentrations in subcutaneous (s.c.) adipose tissue than in intramuscular (i.m.) adipose tissue via G protein-coupled receptor 120 (GPR120). The GPR120 receptor binds to LCFA, which reduces cAMP production, thereby causing a depression in lipolysis. Fresh ex vivo explants of s.c. and i.m. adipose tissue from the fifth to eighth longissimus thoracic rib muscle section of 8, 22-mo-old Angus crossbred steers were transferred immediately to 6-well culture plates containing 3 mL of Krebs-Henseleit buffer/Hepes/5 mM glucose. Samples were preincubated with 0.5 mM theophylline plus 10 mu M forskolin for 30 min, after which increasing concentrations of acetate or propionate (volatile fatty acids, VFA) (0, 1, 5, and 10 mM) in the absence or presence of 100 mu M oleate (18:1n-9) or 100 mu M palmitate (16:0) (LCFA) were added to the incubation media and incubated an additional 30 min. Main effects of adipose tissue depot (i.m. vs. s.c) and VFA (acetate vs. propionate) for adipose tissue concentrations of forskolin-stimulated cAMP were P = 0.747 and P = 0.106, respectively. The addition of LCFA to the media depressed adipose tissue concentrations of cAMP (P = 0.006) (LCFA main effects). The Tissue x VFA x LCFA interaction was not significant for any dependent variable (P >= 0.872). Therefore, concentrations of cAMP, glycerol, and FFA were analyzed separately for i.m. and s.c. adipose tissue by split-plot analysis. Concentrations of cAMP, glycerol, or FFA in i.m. and s.c. adipose tissue were not affected by increasing concentrations of VFA (P >= 0.497). Media LCFA had no effect on i.m. adipose tissue cAMP (P = 0.570) or glycerol (P = 0.470) but depressed i.m. adipose tissue FFA (P < 0.001). In s.c. adipose tissue, LCFA decreased concentrations of cAMP (P = 0.042) and glycerol (P = 0.038), but increased FFA concentration (P = 0.026). Expression of GPR120 (P = 0.804) and stearoyl-CoA desaturase (P = 0.538) was not different between s.c. adipose tissue and i.m. adipose tissue. The binding of VFA to the GPR43 receptor depresses cAMP production, thereby attenuating lipolysis, but GPR43 mRNA was undetectable in those adipose tissue samples. These results provide evidence for functional GPR120 receptors in s.c. adipose tissue but question the role of GPR43 in the accumulation of adipose tissue lipids in growing steers.

본 연구는 3T3-L1 지방세포에서 5종 개별추출물 및 혼합추출물의 항비만 효과를 분석하였다. 개별추출물 중 감잎과 연잎, 도라지추출물에서 지방축적량이 유의적으로 감소했으며, 세포독성을 나타내지 않는 범위 내에서 연잎과 도라지추출물의 감소 효과가 가장 뛰어났다. 이 두 가지 추출물의 상승작용을 확인하기 위해 혼합추출물의 지방 감소 효과를 평가하였다. 연잎추출물과 도라지추출물의 비율이 1:5일 경우, 복합추출물 300μg/mL까지 농도의존적으로 지방축적량이 감소했다. 연잎과 도라지 혼합추출물은 지방산 합성과 관련된 FAS의 발현을 감소시키고 열발생과 관련된 UCP1의 발현이 증가하는 결과를 바탕으로 지방 합성 억제와 에너지 소비를 통한 지방축적량을 감소시키는 것으로 판단된다. 따라서 연잎과 도라지 혼합추출물은 체지방 감소 기능성소재로써 활용 가치가 매우 높을 것으로 예상된다. The continuous increase in obesity necessitates innovative preventive measures. Plant extracts from Diospyros kaki L. (DE), Nelumbo nucifera L. (NE), Rosa canina (RE), Chrysanthemum morifolium (CE), and Platycodon grandiflorus (PE) have been traditionally consumed for medicinal purposes in Asia and Europe. In this study, we evaluated the anti-obesity effects of plant extracts. Fat accumulation was inhibited by PE, DE, and NE in a dose-dependent manner. NE was further mixed at ratios of 1:1-1:5 with PE, and a mixture of 300 μg/mL showed no less reduction in cellular fat than 600 μg/mL of the mixture. Representative enzymes related to lipogenesis and thermogenesis were evaluated. FAS was reduced, whereas uncoupling-protein 1 (UCP1) was enhanced in adipocytes up to 300 μg/mL of a mixture. In conclusion, the combined extract of NE and PE (1:5) is a potent nutraceutical with anti-obesity effects.

[This corrects the article DOI: 10.1007/s10068-023-01464-1.].

SCOPE:Mild cognitive impairment is associated with a high prevalence of dementia. The study examines the benefits of a modified Korean MIND (K-MIND) diet and explores biomarkers using multi-omics analysis. METHODS AND RESULTS:The K-MIND diet, tailored to the elderly Korean population, includes perilla oil, milk, or fermented milk, and avoids alcohol consumption. As a result, the K-MIND diet significantly improves subjects "orientation to place" in the Korean version of the Mini-Mental State Examination, 2nd edition test. According to multi-omics analysis, the K-MIND diet upregulates genes associated with mitochondrial respiration, including ubiquinone oxidoreductase, cytochrome C oxidase, and ATP synthase, and immune system processes, and downregulates genes related to nuclear factor kappa B activity and inflammatory responses. In addition, K-MIND affects the metabolic pathways of glycine, serine, threonine, tryptophan, and sphingolipids, which are closely linked to cognitive function through synthesis of neurotransmitters and structures of brain cell membranes. CONCLUSION:The findings imply that the K-MIND diet improves cognitive function by upregulating key genes involved in oxidative phosphorylation and downregulating pro-inflammatory cytokines.

The American Heart Association suggests that consuming ω-6 fatty acids (5–10% of total energy) can prevent cardiovascular disease by improving lipoprotein profiles. However, some studies warn of deleterious effects of these due to eicosanoid biosynthesis. We explored the five years for clinical evidence of ω-6 fatty acids on several diseases including inflammation, cancer, cardiovascular disease, and metabolic syndrome. Predefined criteria identified a total of 21 articles in 5 databases. Some studies indicated that dietary arachidonic acid was not related to increase of pro-inflammatory cytokines. In cohort studies, ω-6 fatty acids prevented the onset of digestive and lung cancer. ω-6 Fatty acids improved blood lipoprotein profiles. Moreover, consuming ω-6 fatty acids delayed diabetes mellitus and chronic renal disease and had positive effects on muscle recovery and glaucoma. In conclusion, ω-6 fatty acids have beneficial effects on cancers, blood lipoprotein profiles, diabetes, renal disease, muscle function, and glaucoma without inflammation response.

Rottlerin (mallotoxin) is a polyphenolic compound in Mallotus philippensis. The anti-tumor, anti-inflammation, and mitochondrial uncoupling regulation effects of rottlerin have been known. However, the anti-obesity effect was not reported yet. Thus, we hypothesized that rottlerin would suppress body fat accumulation in obesity-induced mice. Five-week-old male C57BL/6 mice were fed a high-fat diet (HFD) (60% kcal from fat) ad libitum for 8 weeks. Mice were randomly assigned to five groups as follows: 1) normal diet (18% kcal from fat), 2) negative control (60% kcal from fat), 3) rottlerin 10 (HFD + rottlerin 10 mg/kg bw), 4) rottlerin 20 (HFD + 20 mg/kg bw), 5) positive control (HFD + metformin 150 mg/kg bw). Rottlerin was daily supplemented by oral gavage. Body weight and feed intake were measured each week. Body weight and weight gain were reduced in rottlerin 20 compared to the control (P < 0.001). Body fat mass was also significantly decreased by rottlerin (P < 0.05). Total feed intake and lean mass were similar among HFD groups. Furthermore, energy expenditure was dose-dependently facilitated by rottlerin. RNA-sequencing results supported these findings that rottlerin 20 up-regulated fatty acid beta-oxidation, heat generation, and brown cell differentiation in white-adipose tissues. Rottlerin promoted a catabolic pathway such as lipolysis, thermogenesis, and oxidation in white adipose tissues. Moreover, non-esterified fatty acid levels were decreased by rottlerin (P < 0.05), and hepatic triglyceride contents tended to decline in rottlerin 20 without hepatotoxicity. Non-shivering thermogenesis enzymes, PRDM16 (P = 0.06) and UCP1 (P < 0.01), were stimulated by rottlerin. Rottlerin supplementation altered body adiposity accumulation via enhancing fat utilization, lipolysis, and thermogenesis in obese mice. We suggest that rottlerin is a potent nutraceutical for anti-obesity. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (Ministry of Science and ICT; MSIT).

Menopause causes ovarian hormone decline, followed by symptoms including weight gain, bone loss, hot flashes, and menopausal depression. We had a purpose that a combination of Leonurus japonicus Houtt, Eclipta prostrata L., and Pueraria lobata Ohwi (LEPE) would alleviate menopausal symptoms in an ovariectomized menopausal rat model. Female rat underwent surgery to resect bilateral ovarian and were randomly assigned to five groups: (1) Sham, (2) Vehicle, negative control, (3) LEPE (100 mg/kg bw), (4) LEPE (200 mg/kg bw), and (5) Estradiol (E2, 3 μg/kg bw). LEPE was orally gavaged daily for 12 weeks. There is no effect on growth performance, including body weight and feed intake, or body composition, including lean mass and fat in tissue. LEPE did not cause hepatotoxicity (aspartate aminotransferase and alanine aminotransferase) and endocrine disturbance (estradiol, follicle-stimulating hormone levels, and uterine weight). Despite decreasing type I collagen (CTX-1), LEPE did not affect bone mineral density and osteocalcin. LEPE supplement reduced the tail temperature and increased the rectal temperature, improving menopause-associated vasomotor symptoms such as hot flashes and night sweat. Furthermore, LEPE relieved behavior related to menopausal depression, including in forced swimming and tail suspension tests. These findings suggest that LEPE ameliorates menopausal symptoms via improving menopause-associated vasomotor symptoms and depression behavior in a female rat model of surgical menopause. This research was funded by Nong Shim.

The prevalence of neurodegenerative disorders such as dementia is positively correlated to aging. As there is insufficient evidence for the medicinal remedies of dementia, focusing on prevention strategies to use nutraceuticals could provide positive results. Therefore, this systematic review aimed to evaluate the effect of various nutraceuticals on age-associated cognitive decline. Literature was searched using PubMed, EMBASE, Cochrane, and PsycINFO databases with the search terms being nutraceuticals in cognitive dysfunction. The literature was limited to human studies, randomized controlled trials, and a single material. Selection of literature, evaluation of the risk of bias, and assessment of the quality of evidence was conducted independently by two reviewers. We finally included 17 studies of literature after excluding the risk of bias ‘high.’ The evidence was rated ‘high’ quality for both omega-3 fatty acids and vitamin Bs. Other materials, including vitamins D & E, anserine/carnosine, and chromium were identified as ‘moderate’ quality. Omega-3 fatty acids (0.48–2.2 g of DHA and 203–720 mg of EPA) relieved cognitive decline and amyloid β related proteins in participants with mild cognitive impairment. However, the cognitive decline did not have an effect on dementia patients. Vitamin B (25–500 µg of B12 and 20 mg of B6) group exhibited decreased homocysteine levels, followed by enhanced cognitive function. However, vitamin D & E, anserine/carnosine, and chromium showed a shred of limited evidence owing to limited studies. This study suggests that omega-3 fatty acids and vitamin B have protective effects against age-associated cognitive decline. This research was funded by Ottogi, grant number HY-201900000670003.

Menopause leads to ovarian hormone loss, which causes symptoms such as weight gain, hot flashes, and depression. Exploring nutraceuticals is important for treating menopausal symptoms that extensively impact women's quality of life. We hypothesized that a combination of Leonurus japonicus Houtt, Eclipta prostrata L., and Pueraria lobata Ohwi (LEPE) would alleviate menopausal symptoms in an ovariectomized menopausal rat model. Bilateral ovariectomy was performed and animals were assigned to five groups: (1) Sham, (2) Vehicle, (-) Control, (3) LEPE (100 mg/kg bw), (4) LEPE (200 mg/kg bw), and (5) Estradiol (3 μg/kg bw). LEPE was orally administered daily for 12 weeks. LEPE supplementation did not affect growth performance (body weight and feed intake) or body composition (lean mass and fat in tissue). LEPE did not cause deviations in aspartate aminotransferase, alanine aminotransferase, estradiol, and follicle-stimulating hormone levels, indicating no hepatotoxicity or endocrine disturbance. LEPE decreased type I collagen (CTX-1) but did not affect bone mineral density or osteocalcin. LEPE decreased tail temperature and increased rectal temperature, improving menopause-related vasomotor symptoms. Furthermore, LEPE ameliorated depression-related behavior, including in forced swimming and tail suspension tests. Thus, LEPE may improve menopausal symptoms by enhancing vasomotor symptoms and depression in an ovariectomized rat menopause model.

Obesity is a notable risk factor for developing type 2 diabetes, augmenting the concern of obese diabetes (ObD). Anti-obesity and antioxidant effects of red pepper seeds extract (RPSE) have increased our expectations that RPSE would also improve the pathological phenotypes of obese diabetes. Therefore, we hypothesized that RPSE would have an anti-diabetic effect in ObD mice. Animals were assigned either as follows: (1) db/+, (2) db/db control, (3) RPSE (200 mg/kg bw), or (4) a comparative control (metformin 150 mg/kg bw). RPSE was orally administered daily for 8 weeks. As a result, RPSE supplementation improved diabetic phenotypes, including fasting glucose, hemoglobin (HbA1c), and insulin levels. Pro-inflammatory cytokines, tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6), and triglycerides were reduced in RPSE-treated mice. RPSE supplementation also diminished the rate-limiting enzymes of gluconeogenesis, including glucose 6-phosphatas (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK), in the liver. RPSE supplementation increased the phosphorylation of forkhead box protein O1 (FOXO1) and AMP-activated protein kinase (AMPK), which underlined the mechanism of the anti-diabetic effects of RPSE. Taken together, RPSE has the potential to improve glycemic control by repressing hepatic gluconeogenesis via the phosphorylation of FOXO1 and AMPK in ObD mice.